Cancer treatment

Abstract

This invention is a method of treating cancer, including carcinomas and sarcomas through the administration of a pharmaceutical composition containing a pyridinylimidazole carbamate. The pyridinylimidazole carbamate is selected from the group consisting of: wherein X is independently selected from the group consisting of halo, for example, bromo, fluoro, chloro, iodo; hydroxyl, alkyl of less than 8 carbon atoms or alkoxy of less than 8 carbon atoms; n is a positive integer less than 4; R is hydrogen or an alkyl group of from 1 to 8 carbons and its pharmaceutically acceptable salts and prodrugs thereof.

What is claimed is:  
     
         1 . A method of treating cancer comprising administering to a patient in need hereof a therapeutically effective amount of a composition comprising a pyridinylimidazole carbamate of the formula:  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from the group consisting of halo, hydroxyl, alkyl of less than 8 carbon atoms or alkoxy of less than 8 carbon atoms; n is a positive integer less than 4; R and R 1  are independently selected from hydrogen or an alkyl group of from 1 to 8 carbons and its pharmaceutically acceptable salts and prodrugs thereof.  
     
     
         2 . A method according to  claim 1  wherein said cancer is prostate cancer.  
     
     
         3 . A method according to  claim 1  wherein said cancer is breast cancer.  
     
     
         4 . A method according to  claim 1  wherein said cancer is colon cancer.  
     
     
         5 . A method according to  claim 1  wherein said cancer is lung cancer.  
     
     
         6 . A method according to  claim 1  wherein said cancer is pancreatic cancer.  
     
     
         7 . A method according to  claim 1  wherein said cancer is ovarian cancer.  
     
     
         8 . A method according to  claim 1  wherein said cancer is a sarcoma.  
     
     
         9 . A method according to  claim 1  wherein said cancer is a lymphoma.  
     
     
         10 . A method according to  claim 1  wherein said pyridinylimidazole carbamate is  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable acid salts or prodrugs thereof.  
     
     
         11 . A method according to  claim 10  wherein said pharmaceutically acceptable salt is a hydrochloride salt.  
     
     
         12 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a combination therapy comprising (1) a pyridinylimidazole carbamate of the formula:  
       
         
           
           
               
               
           
         
       
       wherein X is selected from the group consisting of hydrogen, bromo, fluoro, chloro, iodo, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms; n is a positive integer les the 4, and R is hydrogen or an alkyl group of from 1 to 8 carbon atoms and R 1  is aliphatic hydrocarbon of less than 7 carbon atoms or its pharmaceutically acceptable salts or prodrugs thereof and (2) a safe and effective amount of a chemotherapeutic agent.  
     
     
         13 . A method according to  claim 12  wherein said cancer is prostate cancer.  
     
     
         14 . A method according to  claim 12  wherein said cancer is ovarian cancer.  
     
     
         15 . A method according to  claim 12  wherein said cancer is pancreatic cancer.  
     
     
         16 . A method according to  claim 12  wherein said cancer is breast cancer.  
     
     
         17 . A method according to  claim 12  wherein said cancer is lung cancer.  
     
     
         18 . A method according to  claim 12  wherein said cancer is colon cancer.  
     
     
         19 . A method according to  claim 12  wherein said pyridinylimidazole carbamate is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein X is hydrogen; n is a positive integer less than 4; R and R 1  are hydrogen or an alkyl group of from 1 to 4 carbons and pharmaceutically acceptable salts and prodrugs thereof.  
     
     
         20 . A method according to  claim 19  wherein said chemotherapeutic agent is selected from the group consisting of a DNA-interactive agent, alkylating agent, antimetabolitc, tubulin-interactive agent, hormonal agent, Asparaginase and hydroxyurea.  
     
     
         21 . A method according to  claim 19  wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase, hydroxyurea, Cisplatin, Cyclophosphamide, Altretamine, Bleomycin, Dactinomycin, Doxorubicin, Etoposide, Teniposide, paclitaxel, cytoxan, 2-methoxycarbonylaminobenzimidazole carbamate and Plicamycin.  
     
     
         22 . A method according to  claim 19  wherein said chemotherapeutic agent is selected from the group consisting of Methotrexate, Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine, Floxuridine, Mercaptopurine, 6-Thioguanine, Pentostatin, Cytarabine, and Fludarabine.  
     
     
         23 . A method according to  claim 19  further comprising a safe and effective amount of a potentiator.  
     
     
         24 . A method according to  claim 23 , wherein said potentiator is selected from the group consisting of procodazole, triprolidine, propionic acid, monensin, an anti-sense inhibitor of the RAD51 gene, bromodeoxyuridine, dipyridamole, indomethacin, a monoclonal antibody, an anti-transferrin receptor immunotoxin, metoclopramide, 7-thia-8-oxoguanosine, N-solanesyl-N,N′-bis(3,4-dimethoxybenzyl)ethylenediamine, N-[4-[(4-fluorphenyl)sulfonly]phenyl] acetamide, leucovorin, heparin, heparin sulfate, cimetidine, a radiosensitizer, a chemosensitizer, a hypoxic cell cytotoxic agent, muramyl dipeptide, vitamin A, 2′-deoxycoformycin, a bis-diketopiperazine derivative, and dimethyl sulfoxide.  
     
     
         25 . A pharmaceutical composition comprising a therapeutically effective amount of a composition comprising a pyridinylimidazole carbamate selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from the group consisting of halo, hydrogen, hydroxyl, alkyl of less than 8 carbon atoms or alkoxy of less than 8 carbon atoms; n is a positive integer less than 4; R and R 1  is hydrogen or an alkyl group of from 1 to 8 carbons and its pharmaceutically acceptable salts and prodrugs thereof.  
     
     
         26 . A pharmaceutical composition of  claim 25  further comprising a pharmaceutical carrier.  
     
     
         27 . A pharmaceutical composition according to  claim 26  comprising a pharmaceutical carrier and a safe and effective amount of a potentiator.  
     
     
         28 . A pharmaceutical composition according to  claim 27 , wherein said potentiator is selected from the group consisting of procodazole, triprolidine, propionic acid, monensin, an anti-sense inhibitor of the RAD51 gene, bromodeoxyuridine, dipyridamole, indomethacin, a monoclonal antibody, an anti-transferrin receptor immunotoxin, metoclopramide, 7-thia-8-oxoguanosine, N-solanesyl-N,N′-bis(3,4-dimethoxybenzyl)ethylenediamine, N-[4[(4-fluorphenyl)sulfonly]phenyl] acetamide, leucovorin, heparin, heparin sulfate, cimetidine, a radiosensitizer, a chemosensitizer, a hypoxic cell cytotoxic agent, muramyl dipeptide, vitamin A, 2′-deoxycoformycin, a bis-diketopiperazine derivative, and dimethyl sulfoxide.  
     
     
         29 . A pharmaceutical composition according to  claim 25  further comprising a safe and effective amount of a chemotherapeutic agent.  
     
     
         30 . A pharmaceutical composition according to  claim 29  wherein said chemotherapeutic agent is selected from the group consisting of a DNA-interactive agent, alkylating agent, antimetabolite, tubulin-interactive agent, hormonal agent, Asparaginase and hydroxyurea.  
     
     
         31 . A pharmaceutical composition according to  claim 29  wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase, hydroxyurea, Cisplatin, Cyclophosphamide, Altretamine, Bleomycin, Dactinomycin, Doxorubicin, Etoposide, Teniposide, Paclitaxel, cytoxan, 2-methoxycarbonylaminobenzimidazole carbamate and Plicamycin.  
     
     
         32 . A pharmaceutical composition according to  claim 29  wherein said chemotherapeutic agent is selected from the group consisting of Methotrexate, Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine, Floxuridine, Mercaptopurine, 6-Thioguanine, Pentostatin, Cytarabine, and Fludarabine.  
     
     
         33 . A pharmaceutical composition according to  claim 29  further comprising a safe and effective amount of a potentiator.  
     
     
         34 . A pharmaceutical composition according to  claim 33 , wherein said potentiator is selected from the group consisting of procodazole, triprolidine, propionic acid, monensin, an anti-sense inhibitor of the RAD51 gene, bromodeoxyuridine, dipyridamole, indomethacin, a monoclonal antibody, an anti-transferrin receptor immunotoxin, metoclopramide, 7-thia-8-oxoguanosine, N-solanesyl-N,N′-bis(3,4-dimethoxybenzyl)ethylenediamine, N-[4-[(4-fluorphenyl)sulfonly]phenyl] acetamide, leucovorin, heparin, heparin sulfate, cimetidine, a radiosensitizer, a chemosensitizer, a hypoxic cell cytotoxic agent, muramyl dipeptide, vitamin A, 2′-deoxycoformycin, a bis-diketopiperazine derivative, and dimethyl sulfoxide.  
     
     
         35 . A liposome composition comprising a pyridinylimidazole carbamate selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from the group consisting of hydrogen, bromo, fluoro, chloro, iodo and alkyl of less than 4 carbon atoms or alkoxy of less than 4 carbon atoms; n is a positive integer less than 4; R is hydrogen or an alkyl of less than 7 carbon atoms and its pharmaceutically acceptable salts and prodrugs thereof.  
     
     
         36 . A liposome composition according to  claim 35  selected from the group of consisting of unilamallar vesicle and multilamaller vesicles.  
     
     
         37 . A liposome composition according to claims  36  formed from phospholipids cholesterol, stearylamine or phosphatidyl choline.  
     
     
         38 . A pharmaceutical composition comprising the hydrochloride salt of a pyridinylimidazole carbamate compound having the structure:  
       
         
           
           
               
               
           
         
       
       wherein X is hrdrogen, n is 3, R is hydrogen and R 1  is methyl or ethyl and prodrugs thereof.