US2002151503A1PendingUtilityA1
Methods of cancer treatment using naaladase inhibitors

Priority: Jun 17, 1996Filed: Jan 28, 2002Published: Oct 17, 2002
Est. expiryJun 17, 2016(expired)· nominal 20-yr term from priority
Inventors:Barbara Slusher Paul F. Jackson Kevin L. Tays Keith M. Maclin
A61P 35/00A61K 31/661A61P 43/00C07F 9/3826A61K 31/664A61K 31/675A61K 31/662A61K 31/67A61K 31/66C07F 9/301C07F 9/3808A61K 31/665A61K 31/00A61K 38/05
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References
Claims
Abstract

The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel methods of using phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives to inhibit N-Acetylated α-Linked Acidic Dipeptidase (NAALADase) enzyme activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.
Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating cancer in an animal which comprises: administering to an animal suffering from a cancer an effective amount of a NAALADase inhibitor.  
     
     
         2 . The method of  claim 1  wherein the NAALADase inhibitor is selected from the group consisting of: a glutamate-derived hydroxyphosphinyl derivative compound; an acidic peptide analog; a conformationally restricted glutamate mimic; and mixtures thereof.  
     
     
         3 . The method of  claim 2  wherein the acidic peptide analog is selected from the group consisting of: Asp-Glu, Glu-Glu, Gly-Glu, gamma-Glu-Glu, and Glu-Glu-Glu.  
     
     
         4 . The method of  claim 2  wherein the conformationally restricted glutamate mimic is selected from the group consisting of beta-NAAG and quisqualic acid.  
     
     
         5 . The method of  claim 2  wherein the NAALADase inhibitor is a glutamate-derived hydroxyphosphinyl derivative compound.  
     
     
         6 . The method of  claim 1  wherein the NAALADase inhibitor is administered in combination with an additional therapeutic agent selected from the group consisting of: therapeutic hormones, chemotherapeutic hormones, anti-angiogenesis agents, radiolabelled compounds, and mixtures thereof.  
     
     
         7 . The method of  claim 1  wherein the cancer is selected from the group consisting of: ACTH-producing tumors, acute lymphocytic leukemia, acute nonlymphocytic leukemia, cancer of the adrenal cortex, bladder cancer, brain cancer, breast cancer, cervical cancer, chronic lymphocytic leukemia, chronic myelocytic leukemia, colorectal cancer, cutaneous T-cell lymphoma, endometrial cancer, esophageal cancer, Ewing&#39;s sarcoma, gallbladder cancer, hairy cell leukemia, head &amp; neck cancer, Hodgkin&#39;s lymphoma, Kaposi&#39;s sarcoma, kidney cancer, liver cancer, lung cancer, lung cancer (small and/or non-small cell), malignant peritoneal effusion, malignant pleural effusion, melanoma, mesothelioma, multiple myeloma, neuroblastoma, non-Hodgkin&#39;s lymphoma, osteosarcoma, ovary cancer, ovary (germ cell) cancer, pancreatic cancer, penis cancer, prostate cancer, retinoblastoma, skin cancer, soft tissue sarcoma, squamous cell carcinomas, stomach cancer, testicular cancer, thyroid cancer, trophoblastic neoplasms, cancer of the uterus, vaginal cancer, cancer of the vulva, and Wilm&#39;s tumor.  
     
     
         8 . The method of  claim 1  wherein the cancer is prostatic adenocarcinoma.  
     
     
         9 . The method of  claim 1  wherein the cancer is selected from the group consisting of: brain cancer, cancer of the adrenal cortex, kidney cancer, and testicular cancer.  
     
     
         10 . The method of  claim 1  wherein the NAALADase inhibitor comprises a compound having the following formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is hydrogen, C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 ;  
 X is CH 2 , O, or NR 1 , where R 1  is defined above; and  
 R 2  is C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl group may be optionally substituted with carboxylic acid, 
 wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl groups may be optionally substituted with C 3 -C 8  cycloalkyl, C 3  or C 5  cycloalkyl, C 5 -C 7  cycloalkenyl, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched chain alkyl or alkenyl, C 1 -C 4  alkoxy, C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, amino, or Ar 1 , and where Ar 1  is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 4-indolyl, 2-furyl, 3-furyl, tetrahydrofuranyl, 2-thienyl, 3-thienyl, 4-thienyl, 2-, 3-, or 4-pyridyl, or phenyl, having one to five substituents which are independently selected from the group consisting of hydrogen, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched alkyl or alkenyl, C 1 -C 4  alkoxy or C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, and amino; or pharmaceutically acceptable salts, hydrates, or mixtures thereof.  
 
 
     
     
         11 . The method of  claim 10  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is CH 2 .  
     
     
         12 . The method of  claim 11  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-(methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(cyclohexylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((cyclohexyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylpropylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylbutylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylprop-2-enylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]decanedioic acid;  
 3-(benzylhydroxyphosphinyl)-2-methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-propypropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-cyclohexyipropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(cyclohexyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-benzylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylethyipropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylbutylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2,3,4-trimethoxyphenyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)methylpropancic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylprop-2-enylpropanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[(2-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propylpropanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         13 . The method of  claim 11  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[((hydroy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         14 . The method of  claim 10  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is oxygen.  
     
     
         15 . The method of  claim 14  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phnheylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]oxy]pentanedicic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)butyhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-(phosphono)oxy]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]-2-phenyiethanoic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[(methylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-cyclohexylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylprop-2-enylethanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)mrethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy)-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         16 . The method of  claim 14  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(phosphono)oxy]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         17 . The method of  claim 10  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is NR 1 .  
     
     
         18 . The method of  claim 17  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]-2-pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[cyclchexylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-cyclohexylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenolprop-2-enylethanoic acid;  
 2-[(methylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]decanedioic acid;  
 3-[[(2-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(2-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(2-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-thienyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-thienyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)methylethanoic acid;  
 2-[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)methylethanoic acid;  
 2-[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         19 . The method of  claim 17  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         20 . The method of  claim 10  wherein R 1  or R 2  is heterocyclic and X is CH 2 .  
     
     
         21 . The method of  claim 20  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[(2-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)propanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         22 . The method of  claim 10  wherein R 1  or R 2  is heterocyclic and X is oxygen.  
     
     
         23 . The method of  claim 22  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[tetrahydrofuranyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)ethanoic acid;  
 2-[]benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         24 . The method of  claim 10  wherein R 1  or R 2  is heterocyclic and X is NR 1 .  
     
     
         25 . The method of  claim 24  wherein the NAALADase inhibitor is a compound selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuraryl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         26 . A method of inhibiting tumor cell growth in an animal which comprises: administering to an animal suffering from a tumor cell growth an effective amount of a NAALADase inhibitor.  
     
     
         27 . The method of  claim 26  where the tumor is prostate adenocarcinoma.  
     
     
         28 . The method of  claim 26  wherein the NAALADase inhibitor is selected from the group consisting of: a glutamate-derived hydroxyphosphinyl derivative compound; an acidic peptide analog; a conformationally restricted glutamate mimic; and mixtures thereof.  
     
     
         29 . The method of  claim 28  wherein the acidic peptide analog is selected from the group consisting of: Asp-Glu, Glu-Glu, Gly-Glu, gamma-Glu-Glu, and Glu-Glu-Glu.  
     
     
         30 . The method of  claim 28  wherein the conformationally restricted glutamate mimic is selected from the group consisting of: beta:NAAG and quisqualic acid.  
     
     
         31 . The method of  claim 28  wherein the NAALADase inhibitor is a glutamate-derived hydroxyphosphinyl derivative compound.  
     
     
         32 . The method of  claim 26  wherein the NAALADase inhibitor is administered in combination with an additional therapeutic agent selected from the group consisting of: therapeutic hormones, chemotherapeutic hormones, anti-angiogenesis agents, radiolabelled compounds, and mixtures thereof.  
     
     
         33 . The method of  claim 26  wherein the tumor is selected from the group consisting of: ACTH-producing tumor, acute lymphocytic leukemia, acute nonlymphocytic leukemia, cancer of the adrenal cortex, bladder cancer, brain cancer, breast cancer, cervical cancer, chronic lymphocytic leukemia, chronic myelocytic leukemia, colorectal cancer, cutaneous T-cell lymphoma, endometrial cancer, esophageal cancer, Ewing&#39;s sarcoma, gallbladder cancer, hairy cell leukemia, head &amp; neck cancer, Hodgkin&#39;s lymphoma, Kaposi&#39;s sarcoma, kidney cancer, liver cancer, lung cancer, lung cancer (small and/or non-small cell), malignant peritoneal effusion, malignant pleural effusion, melanoma, mesothelioma, multiple myeloma, neuroblastoma, non-Hodgkin&#39;s lymphoma, osteosarcoma, ovary cancer, ovary (germ cell) cancer, pancreatic cancer, penis cancer, prostate adenocarcinoma, retinoblastoma, skin cancer, soft tissue sarcoma, squamous cell carcinomas, stomach cancer, testicular cancer, thyroid cancer, trophoblastic neoplasms, cancer of the uterus, vaginal cancer, cancer of the vulva, and Wilm&#39;s tumor.  
     
     
         34 . The method of  claim 26  wherein the tumor is prostatic adenocarcinoma.  
     
     
         35 . The method of  claim 26  wherein the tumor is selected from the group consisting of: brain cancer, cancer of the adrenal cortex, kidney cancer, and testicular cancer.  
     
     
         36 . The method of  claim 26  wherein the NAALADase inhibitor comprises a compound having the following formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is hydrogen, C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 ;  
 X is CH 2 , O, or NR 1 , where R 1  is defined above; and  
 R 2  is C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl group may be optionally substituted with carboxylic acid,  
 wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl groups may be optionally substituted with C 3 -C 8  cycloalkyl, C 3  or C 5  cycloalkyl, C 1 -C 7  cycloalkenyl, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched chain alkyl or alkenyl, C 1 -C 4  alkoxy, C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, amino, or Ar 1 , and where Ar 1  is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 4-indolyl, 2-furyl, 3-furyl, tetrahydrofuranyl, 2-thienyl, 3-thienyl, 4-thienyl, 2-, 3-, or 4-pyridyl, or phenyl, having one to five substituents which are independently selected from the group consisting of hydrogen, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched alkyl or alkenyl, C 1 -C 4  alkoxy , C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, and amino; or pharmaceutically acceptable salts, hydrates, or mixtures thereof.  
 
     
     
         37 . The method of  claim 36  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is CH 2 .  
     
     
         38 . The method of  claim 37  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-(methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(cyclohexylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((cyclohexyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylpropylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylbutylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylprop-2-enylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]decanedioic acid;  
 3-(benzylhydroxyphosphinyl)-2-methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-cyclohexylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(cyclohexyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-benzylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylbutylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2,3,4-trimethoxyphenyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylprop-2-phenylpropanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[[(2-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(4-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-pyridyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-pyridyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(2-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(4-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-indolyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-indolyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(2-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(4-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[[(3-thienyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propylpropanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         39 . The method of  claim 37  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         40 . The method of  claim 36  wherein R 1  and R 2  are straight or branched or carbocyclic groups and X is oxygen.  
     
     
         41 . The method of  claim 40  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl))butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(phosphono)oxy]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl)]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[(methylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-cyclohexylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylprop-2-enylethanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl3oxy]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         42 . The method of  claim 40  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(phosphono)oxy]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         43 . The method of  claim 36  wherein R 1  and R 2  are straight or branched or carbocyclic and X is NR 1 .  
     
     
         44 . The method of  claim 43  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2 3,4-trimethoxyphenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-([(2-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[cyclohexylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl)]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl}propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-cyclohexylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethylethanoic acid;  
 2-[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenolprop-2-enylethanoic acid;  
 2-[(methylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]decanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         45 . The method of  claim 43  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         46 . The method of  claim 36  wherein R 1  or R 2  is heterocyclic and X is CH 2 .  
     
     
         47 . The method of  claim 46  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[(2-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl2-(2-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)propanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         48 . The method of  claim 36  wherein R 1  or R 2  is heterocyclic and X is oxygen.  
     
     
         49 . The method of  claim 48  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         50 . The method of  claim 36  wherein R 1  or R 2  is heterocyclic and X is NR 1 .  
     
     
         51 . The method of  claim 50  wherein the NAALADase inhibitor is a compound selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         52 . A method of inhibiting NAALADase enzyme activity in an animal which comprises: administering to an animal suffering from a disorder related to NAALADase enzyme activity an effective amount of a NAALADase inhibitor.  
     
     
         53 . The method of  claim 52  wherein the NAALADase inhibitor is selected from the group consisting of: a glutamate-derived hydroxyphosphinyl derivative compound; an acidic peptide analog; a conformationally restricted glutamate mimic; and mixtures thereof.  
     
     
         54 . The method of  claim 53  wherein the acidic peptide analog is selected from the group consisting of: Asp-Glu, Glu-Glu, Gly-Glu, gamma-Glu-Glu, and Glu-Glu-Glu.  
     
     
         55 . The method of  claim 53  wherein the conformationally restricted glutamate mimic is selected from the group consisting of: beta:NAAG and quisqualic acid.  
     
     
         56 . The method of  claim 53  wherein the NAALADase inhibitor is a glutamate-derived hydroxyphosphinyl derivative compound.  
     
     
         57 . The method of  claim 52  wherein the NAALADase inhibitor is administered in combination with an additional therapeutic agent selected from the group consisting of: therapeutic hormones, chemotherapeutic hormones, anti-angiogenesis agents, radiolabelled compounds, and mixtures thereof.  
     
     
         58 . The method of  claim 52  wherein the disorder related to NAALADase enzyme activity is prostate disease wherein the prostate disease is selected from the group consisting of prostate cancer and benign prostatic hyperplasia.  
     
     
         59 . The method of  claim 52  wherein the NAALADase inhibitor comprises a compound having the following formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is hydrogen, C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 ;  
 X is CH 2 , O, or NR 1 , where R 1  is defined above; and  
 R 2  is C 1 -C 9  straight or branched chain alkyl, C 2 -C 9  straight or branched chain alkenyl group, C 3 -C 8  cycloalkyl, C 5 -C 7  cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl group may be optionally substituted with carboxylic acid, 
 wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl groups may be optionally substituted with C 3 -C 8  cycloalkyl, C 3  or C 5  cycloalkyl, C 5 -C 7  cycloalkenyl, C 1 -C 4  alkyl, C 1 -C 4  alkenyl, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched chain alkyl or alkenyl, C 1 -C 4  alkoxy, C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, amino, or Ar 1 , and where Ar 1  is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 4-indolyl, 2-furyl, 3-furyl, tetrahydrofuranyl, 2-thienyl, 3-thienyl, 4-thienyl, 2-, 3-, or 4-pyridyl, or phenyl, having one to five substituents which are independently selected from the group consisting of hydrogen, halo, hydroxy, carboxy, nitro, trifluoromethyl, C 1 -C 6  straight or branched alkyl or alkenyl, C 1 -C 4  alkoxy or C 1 -C 4  alkenyloxy, phenoxy, benzyloxy, and amino; or pharmaceutically acceptable salts, hydrates, or mixtures thereof.  
 
 
     
     
         60 . The method of  claim 59  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is CH 2 .  
     
     
         61 . The method of  claim 60  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-(methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(cyclohexylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((cyclohexyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylpropylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylbutylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)hydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)methylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)ethylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)propylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((1-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-((2-naphthyl)butylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(phenylprop-2-enylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]nonanedioic acid;  
 2-[(methylhydrcxyphosphinyl)methyl]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)methyl]decanedioic acid;  
 3-(benzylhydroxyphosphinyl)-2-methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-cyclohexylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(cyclohexyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-benzylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylpropylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylbutylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2,3,4-trimethoxyphenyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(1-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-naphthyl)butylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-phenylprop-2-enyl propanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[(2-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-pyridyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)methylhydroxyphosphinyl]2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-indolyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-thienyl)methylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)ethylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)propylhydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)methylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)ethylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propylpropanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         62 . The method of  claim 60  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)methyl]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-(phosphonomethyl)pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]methyl]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         63 . The method of  claim 59  wherein R 1  and R 2  are straight or branched aliphatic groups or carbocyclic groups and X is oxygen.  
     
     
         64 . The method of  claim 63  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(((hydroxy)phenylmethyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(phosphono)oxy]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[cyclohexylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-naphthyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl)]oxy]-2-phenylethanoic acid;  
 2-[[(3-naphthyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-naphthyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-naphthyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-naphthyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-naphthyl)butylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[(methylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)oxy]decanedioic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-phenylprop-2-enylethanoic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]oxy]2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)methylethanoic acid;  
 2-[[(benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         65 . The method of  claim 63  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)oxy]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[(phosphono)oxy]pentanedioic acid; 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]oxy]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         66 . The method of  claim 59  wherein R 1 and R   2  are straight or branched aliphatic groups or carbocyclic and X is NR 1 .  
     
     
         67 . The method of  claim 66  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[cyclohexylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2,3,4-trimethoxyphenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(phenylprop-2-enyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[benzylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[cyclohexylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(cyclohexyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylpropylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylbutylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2,3,4-trimethoxyphenyl)-3-hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)methylhydroxyphosphinyl)]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl}propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(1-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-naphthyl)butylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[phenylprop-2-enylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-cyclohexylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(cyclohexyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-benzylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylpropylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenylbutylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2,3,4-trimethoxyphenyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(1-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-naphthyl)butylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-phenolprop-2-enylethanoic acid;  
 2-[(methylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]hexanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]heptanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]octanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]nonanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]decanedioic acid;  
 2-[(benzylhydroxyphosphinyl)amino]decanedioic acid;  
 3-[[(2-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-pyridyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-pyridyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(2-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-indolyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-indolyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(2-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-thienyl)methylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(4-thienyl)methylhydroxyphosphinyl amino]pentanedioic acid;  
 3-[[(3-thienyl)ethylhydroxyphosphinyl]amino]pentanedioic acid;  
 3-[[(3-thienyl)propylhydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)methylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)ethylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)propylhydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrafuranyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)propylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)methylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)propylethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         68 . The method of  claim 66  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[(benzylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[((hydroxy)phenylmethyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(butylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(3-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(3-phenylpropylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-fluorophenyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(methylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[(phenylethylhydroxyphosphinyl)amino]pentanedioic acid;  
 2-[[(4-methylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-methoxybenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-fluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(pentafluorobenzyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[(phosphono)amino]pentanedioic acid;  
 2-[[(3-trifluoromethylbenzyl)hydroxyphosphinyl]amino]pentanedioic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         69 . The method of  claim 59  wherein R 1  or R 2  is heterocyclic and X is CH 2 .  
     
     
         70 . The method of  claim 69  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]methyl]pentanedioic acid;  
 3-[(2-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-pyridyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(tetrahydrofuranyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-indolyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(2-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(3-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-[(4-thienyl)hydroxyphosphinyl]-2-phenylpropanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-pyridyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(tetrahydrofuranyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-indolyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(2-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(3-thienyl)propanoic acid;  
 3-(benzylhydroxyphosphinyl)-2-(4-thienyl)propanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         71 . The method of  claim 69  wherein R 1  or R 2  is heterocyclic and X is oxygen.  
     
     
         72 . The method of claim  71  wherein the NAALADase inhibitor is selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]oxy]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(3-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]oxy]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.  
 
     
     
         73 . The method of  claim 59  wherein R 1  or R 2  is heterocyclic and X is NR 1 .  
     
     
         74 . The method of claim  73  wherein the NAALADase inhibitor is a compound selected from the group consisting of: 
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]pentanedioic acid;  
 2-[[(2-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-pyridyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(tetrahydrofuranyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-indolyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(2-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(3-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[(4-thienyl)hydroxyphosphinyl]amino]-2-phenylethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-pyridyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(tetrahydrofuranyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-indolyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(2-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(3-thienyl)ethanoic acid;  
 2-[[benzylhydroxyphosphinyl]amino]-2-(4-thienyl)ethanoic acid; and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.
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