US2003144509A1PendingUtilityA1
Pyrimidine derivatives and methods of making and using these derivatives
Priority: Apr 8, 1991Filed: Dec 5, 2002Published: Jul 31, 2003
Est. expiryApr 8, 2011(expired)· nominal 20-yr term from priority
Inventors:Aleem Gangjee
C07D 493/04C07D 239/95C07D 471/04A61P 35/00C07D 487/04
54
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Claims
Abstract
This invention discloses compounds, and pharmaceutically acceptable salts thereof, useful in therapeutically and/or prophylactically treating patients with an illness. Such illnesses include cancer, and secondary infections caused by Pneumocystis carinii and Toxoplasmosis gondii in immunocompromised patients. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and
where Z 2 is R 4 when Z 1 is
and Z 2 is
when Z 3 is R 4 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of CH, nitrogen, N—CH 2 , CH 2 —N, CH 2 —CH 2 , oxygen and sulfur;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is oxygen or sulfur;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group;
wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group;
wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen;
wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a-lower alkyl group and R 4 is hydrogen;
wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, and mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero;
wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; and
wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons.
2 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is hydrogen, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is selected from the group consisting of 1-naphthyl and 4-hydroxyphenyl.
3 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is methyl, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is selected from the group consisting of 2,5-dimethoxyphenyl, 3,4-dichlorophenyl and 1-naphthyl.
4 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a double bond, A is CH, B is sulfur, R 1 is zero, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is selected from the group consisting of 3,4-dimethoxyphenyl, 3,4-dichlorophenyl, 1-naphthyl and 2-naphthyl.
5 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is methyl, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is p-benzoyl-L-glutamate.
6 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is OH, Y is NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is hydrogen, R 3 is hydrogen, R 4 is methyl, R 5 is hydrogen and R 8 is p-benzoyl-L-glutamate.
7 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is OH, Y is NH 2 , the bond between L and M is a double bond, A is CH, B is sulfur, R 1 is zero, R 3 is hydrogen, R 4 is methyl, R 5 is hydrogen and R 8 is 4-pyridine.
8 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is OH, Y is NH 2 , the bond between L and M is a double bond, A is zero, B is sulfur, R 1 is zero, R 3 is zero, R 4 is methyl, R 5 is hydrogen and R 8 is selected from the group consisting of 3,4-dimethoxyphenyl, 3,4-dichlorophenyl, 4-chlorophenyl, 4-NO2phenyl, phenyl and 2-naphthyl.
9 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is OH, Y is NH 2 , the bond between L and M is a double bond, A is CH, B is N—CH 2 , R 1 is hydrogen, R 3 is hydrogen, R 4 is methyl, R 5 is hydrogen and R 8 is p-benzoyl-L-glutamate.
10 . The compound, and pharmaceutically acceptable salts thereof, of claim 1 , wherein X is OH, Y is NH 2 , the bond between L and M is a double bond, A is CH, B is CH, R 1 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is selected from the group consisting of thiophenyl, 1-thionaphthyl and 2-thionaphthyl.
11 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and where Z 2 is R 4 when Z 3 is and Z 2 is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N—CH 2 , CH2—N, CH 2 —CH 2 , oxygen and sulfur; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is oxygen or sulfur; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
12 . The method of claim 11 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is methyl, R 3 is hydrogen, R 4 is hydrogen, R 5 is hydrogen and R 8 is p-benzoyl-L-glutamate.
13 . The method of claim 11 , wherein X is NH 2 , Y is NH 2 , A is zero, B is sulfur, R 1 is zero, R 3 is zero, R 4 is hydrogen, R 5 is hydrogen and R 8 is phenyl.
14 . The method of claim 11 , wherein said illness is cancer.
15 . The method of claim 11 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
16 . The method of claim 11 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
17 . The method of claim 11 , including administering said compound incorporated in said carrier to a patient parenterally.
18 . The method of claim 11 , including administering said compound incorporated in said carrier to a patient orally.
19 . The method of claim 11 , including administering said compound incorporated in said carrier to a patient topically.
20 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 2 and Z 3 are different and are selected from the group consisting of R 4 and where Z 1 is R 4 when Z 3 is and Z 2 is when Z 3 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of CH, nitrogen, N—CH 2 , CH 2 —N, CH 2 —CH 2 ,oxygen and sulfur; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is oxygen or sulfur; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 8 is selected from the group consisting of naphthyl, mono-, di- and tri-substituted-naphthyl, thionaphthyl, thiophenyl and hydroxyphenyl when R 1 is hydrogen and R 4 is hydrogen; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, pyridine and p-aroyl-L-glutamate when R 1 is a lower alkyl group and R 4 is hydrogen; wherein R 8 is selected from the group consisting of pyridine, phenyl, mono-, di- and tri,-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is zero; wherein R 8 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate when R 1 is hydrogen and R 4 is a lower alkyl group; wherein R 8 is not p-benzoyl-L-glutamate or pyridine when X is OH, A is zero, B is sulfur, R 4 is methyl and R 5 is hydrogen, and R 8 is not p-benzoyl-L-glutamate when X is OH, A is CH, B is CH, R 4 is hydrogen and R 5 is hydrogen; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
21 . The method of claim 20 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
22 . The method of claim 20 , including administering said compound incorporated in said carrier to a patient parenterally.
23 . The method of claim 20 , including administering said compound incorporated in said carrier to a patient orally.
24 . The method of claim 20 , including administering said compound incorporated in said carrier to a patient topically.
25 . A method of synthesizing a compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having-from about 1 to 6 carbons, comprising the steps of:
a) debrominating a pyrrole;
b) fusing the product of step a) with an amidine;
c) condensing the product of step b) with a nucleophile;
d) reducing the product of step c); and
e) purifying the compounds of step d).
26 . The method of claim 25 , wherein the debromination of step a) is performed in a mixture of dimethyl formamide (DMF) and methanol under hydrogenation in the presence of a palladium catalyst.
27 . The method of claim 26 , wherein the fusion of step b) is performed with chlorformamidine hydrochloride.
28 . The method of claim 27 , wherein the condensation of step c) is carried out with a nucleophile selected from the group consisting an aniline, diethyl(p-aminoaroyl)-L-glutamate and N-methyl diethyl(p-aminoaroyl)-L-glutamate.
29 . The method of claim 28 , wherein the condensation of step c) is performed in 70-80% acetic acid under hydrogenation, and in the presence of a Raney nickel catalyst.
30 . The method of claim 29 , wherein the fusion of step b) is further performed by heating a uniformly stirred suspension of the product of step a) and chlorformamidine hydrochloride in a liquid heat transfer media and heating to a temperature of between about 150° C. and 180° C. for a period of between about 36 and 50 hours.
31 . The method of claim 30 , wherein the condensation of step c) is further performed with hydrogenation pressures ranging from about 50 to about 60 psi, and the reaction is carried out for a period of between about 24 to 72 hours.
32 . The method of claim 31 , wherein the reduction of step d) is further performed by stirring a solution of the product of step c) in methanol at room temperature with NaCNBH 3 .
33 . The method of claim 32 , wherein the purification of step e) is further performed by a method selected from the group consisting of silica gel column chromatography and dissolution of the product of step d) in methanol, filtration, evaporation of the filtrate, and trituration of the residue in anhydrous diethylether.
34 . The method of claim 28 wherein diethyl(p-amino-benzoyl)-L-glutamate or N-methyl diethyl(p-aminobenzoyl)-L-glutamate is used in the condensation of step c).
35 . The method of claim 28 , wherein said method further includes the step f) hydrolyzing the product of step e).
36 . The method of claim 35 , wherein the hydrolysis of step f) is accomplished by stirring a solution of the product of step e) in a 1:1 sodium hydroxide:methanol solution at room temperature for between about 60 and 84 hours.
37 . The method of claim 25 wherein said lower alkyl group has one to about six carbon atoms branched, unbranched and alicyclic; wherein said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; wherein said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; wherein said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl groups; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy group, chlorine atom, bromine atom and fluorine atom.
38 . The method of claim 25 , wherein R is selected from the group consisting of 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 4-methoxyphenyl, 2,5-diethoxyphenyl, 3,4-dichlorophenyl, 2,3-tetramethylphenyl and phenyl.
39 . The method of claim 28 , wherein said an analine is selected from the group consisting of a compound of the formula
wherein R 6 is selected from the group consisting of 3′,4′,5′-trimethoxy, 3′,4′-dimethoxy, 4′-methoxy, 2′,5′-dimethoxy, 2′,5′-diethoxy, 3′,4′-dichloro, 2′,3′-tetramethyl, hydrogen trimethoxy, dimethoxy and monomethoxy groups, trihalo, dihalo and monohalo groups, trialkyl, dialkyl and monoalkyl groups and combinations of methoxy groups, halo groups and lower alkyls.
40 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, an pharmaceutically acceptable salts thereof, having the formula: wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is-the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a-halogen, wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; which has been synthesized by the steps comprising:
i) debrominating a pyrrole;
ii) fusing the product of step a) with an amidine;
iii) condensing the product of step b) with a nucleophile;
iv) reducing the product of step c); and
v) purifying the compounds of step d);
b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
41 . The method of claim 40 , wherein said illness is cancer.
42 . The method of claim 40 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
43 . The method of claim 40 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
44 . The method of claim 40 , including administering said compound incorporated in said carrier to a patient parenterally.
45 . The method of claim 40 , including administering said compound incorporated in said carrier to a patient orally.
46 . The method of claim 40 , including administering said compound incorporated in said carrier to a patient topically.
47 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein R is selected from the group consisting of a lower alkyl group,, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen, wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; which has been synthesized by the steps comprising:
i) debrominating a pyrrole;
ii) fusing the product of step a) with an amidine;
iii) condensing the product of step b) with a nucleophile;
iv) reducing the product of step c); and
v) purifying the compounds of step d).
b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
48 . The method of claim 47 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
49 . The method of claim 47 , including administering said compound incorporated in said carrier to a patient parenterally.
50 . The method of claim 47 , including administering said compound incorporated in said carrier to a patient orally.
51 . The method of claim 47 , including administering said compound incorporated in said carrier to a patient topically.
52 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z and Z 1 are different and are selected from the group consisting of R 4 and
where Z is R 4 when Z 1 is
and Z is
when Z 1 is R 4 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted-alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl, an alkoxy, an alkoxyaryloxy group, a halogen and zero but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or a p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons.
53 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein said lower alkyl groups are branched, unbranched and alicyclic; said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; wherein said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; wherein said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl groups; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy- group, chlorine atom, bromine atom and fluorine atom.
54 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is CH, B is sulfur, R 1 is zero, R 2 is selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl, R 3 is hydrogen and R 4 is hydrogen.
55 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is hydrogen, R 2 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-phenoxyphenyl, 4-phenoxyphenyl, 2-phenylphenyl, 2′,5′-dichlorophenyl and 3′-methoxyphenyl, R 3 is hydrogen and R 4 is hydrogen.
56 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is CH, B is oxygen, R 1 is zero, R 2 is 2-naphthyl, R 3 is hydrogen and R 4 is hydrogen.
57 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is CH, B is nitrogen, R 1 is methyl, R 2 is selected from the group consisting of 3′,4′-dichlorophenyl and 3′,4′,5′-trichlorophenyl, R 3 is hydrogen and R 4 is hydrogen.
58 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is zero, B is zero, R 1 is zero, R 2 is phenyl, R 3 is zero and R 4 is hydrogen.
59 . The compound, and pharmaceutically acceptable salts thereof, of claim 52 , wherein X and Y are both NH 2 , the bond between L and M is a double bond, A is CH, B is hydrogen, R 1 is zero, R 2 is zero, R 3 is hydrogen and R 4 is S—R 7 wherein R 7 is selected from the group consisting of 1-naphthyl and 2-naphthyl.
60 . A method of synthesizing a compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z and Z 1 are different and are selected from the group consisting of R 4 and
where Z is R 4 when Z 1 is
and Z is
when Z 1 is R 4 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or,,the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero, but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate,; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons, comprising the steps of:
a) stirring a pyrimidine and a substituted acetone in a solvent;
b) purifying the product of step a);
c) performing nucleophilic displacement of the chloride in the product of step b); and
d) purifying the product of step c).
61 . The method of claim 60 , wherein step a) is performed by stirring one equivalent each of 2,6-diamino-4-hydroxypyrimidine and 1,3-dichloroacetone in DMF at room temperature for between about 12 and 36 hours.
62 . The method of claim 61 , wherein the purification of step b) is performed by column chromatography.
63 . The method of claim 62 , wherein the nucleophilic displacement of step c) is performed with a compound selected from the group consisting of (p-aminoaroyl)-L-glutamic acid, diethyl N-[p-(methylamino)-aroyl]glutamate, and an aniline.
64 . The method of claim 63 , wherein step c) is performed with p-amino-benzoyl-L-glutamic acid.
65 . The method of claim 63 , wherein the nucleophilic displacement of step c) is performed with diethyl N-[p-(methylamino) benzoyl]glutamate.
66 . The method of claim 63 , wherein the purification of step d) is performed by precipitating the product of step c) by diluting said product with water and separating said product from unreacted starting materials and impurities by cellulose column chromatography, followed by acidification.
67 . The method of claim 66 , wherein the purification of step d) is accomplished by stirring the product of step c) with 1N sodium hydroxide at room temperature for between about 36 to 50 hours, followed by acidification.
68 . The method of claim 67 , wherein the nucleophilic displacement of step c) is performed with an aniline.
69 . The method of claim 68 , wherein the purification of step d) is accomplished by adding excess water to the reaction mixture of step c) and stirring at room temperature for between about 6 and 8 hours.
70 . The method of claim 69 , wherein said aniline is selected from the group consisting of the formula:
wherein R 6 is selected from the group-consisting of 3′,4′,5′-trimethoxy, 3′,4′-dimethoxy, 4′-methoxy, 2′,5′-dimethoxy, 2′,5′-diethoxy, 3′,4′-dichloro, 2′,3′-tetramethyl, hydrogen trimethoxy, dimethoxy and monomethoxy groups, trihalo, dihalo and monohalo groups, trialkyl, dialkyl and monoalkyl gropus and combinations of methoxy groups, halo gropus and lower alkyls.
71 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z, are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero, but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate; and wherein each-lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons, and is synthesized by the steps:
i) stirring a pyrimidine and a substituted acetone in a solvent;
ii) purifying the product of step a);
iii) performing nucleophilic displacement of the chloride in the product of step b); and
iv) purifying the product of step c);
b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
72 . The method of claim 71 , wherein said illness is cancer.
73 . The method of claim 71 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
74 . The method of claim 71 , wherein X and Y are both NH 2 , A is CH, B is sulfur, R 1 is zero, R 2 is 2-naphthyl, R 3 is hydrogen and R 4 is hydrogen.
75 . The method of claim 71 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
76 . The method of claim 71 , including administering said compound incorporated in said carrier to a patient parenterally.
77 . The method of claim 71 , including administering said compound incorporated in said carrier to a patient orally.
78 . The method of claim 71 , including administering said compound incorporated in said carrier to a patient topically.
79 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a-compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the-group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero, but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, and p-aroyl-L-glutamate; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons, and is synthesized by the steps:
i) stirring a pyrimidine and a substituted acetone in a solvent;
ii) purifying the product of step a);
iii) performing nucleophilic displacement of the chloride in the product of step b); and
iv) purifying the product of step c);
b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
80 . The method of claim 79 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
81 . The method of claim 79 , including administering said compound incorporated in said carrier to a patient parenterally.
82 . The method of claim 79 ,, including administering said compound incorporated in said carrier to a patient orally.
83 . The method of claim 79 , including administering said compound incorporated in said carrier to a patient topically.
84 . The compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z and Z 1 are different and are selected from the group consisting of R 4 and
where Z is R 4 when Z 1 is
and Z is
when Z 1 is R 4 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, an aryl group, p-aroyl-L-glutamate, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons.
85 . The compound, and pharmaceutically acceptable salts thereof, of claim 84 , wherein said lower alkyl groups are branched, unbranched and alicyclic; said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; wherein said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; wherein said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl groups; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy group, chlorine atom, bromine atom and fluorine atom.
86 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
87 . The method of claim 86 , wherein said illness is a cancer.
88 . The method of claim 86 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
89 . The method of claim 86 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
90 . The method of claim 86 , including administering said compound incorporated in said carrier to a patient parenterally.
91 . The method of claim 86 , including administering said compound incorporated in said carrier to a patient orally.
92 . The method of claim 86 , including administering said compound incorporated in said carrier to a patient topically.
93 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
94 . The method of claim 93 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
95 . The method of claim 93 , including administering said compound incorporated in said carrier to a patient parenterally.
96 . The method of claim 93 , including administering said compound incorporated in said carrier to a patient orally.
97 . The method of claim 93 , including administering said compound incorporated in said carrier to a patient topically.
98 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH,;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z and Z 1 are different and are selected from the group consisting of R 4 and
where Z is R 4 when Z 1 is
and Z is
when Z 1 is R 4 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group;
wherein R 5 is selected from the group consisting of hydrogen and lower alkyl group; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons.
99 . The compound, and pharmaceutically acceptable salts thereof, of claim 98 , wherein said lower alkyl groups are branched, unbranched and alicyclic; said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl groups; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy group, chlorine atom, bromine atom and fluorine atom.
100 . The compound, and pharmaceutically acceptable salts thereof, of claim 98 , wherein Y is NH 2 , X is HN2, the bond between L and M is a double bond, B is CH, A is zero, R 1 is hydrogen, R 2 is selected from the group consisting of phenyl and 3,4-dichlorophenyl, R 3 is zero, R 4 is selected from the group consisting of hydrogen and a lower alkyl group; and R 5 is selected from the group consisting of hydrogen and a lower alkyl group.
101 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
102 . The method of claim 101 , wherein said illness is cancer.
103 . The method of claim 101 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
104 . The method of claim 101 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
105 . The method of claim 101 , including administering said compound incorporated in said carrier to a patient parenterally.
106 . The method of claim 101 , including administering said compound incorporated in said carrier to a patient orally.
107 . The method of claim 101 , including administering said compound incorporated in said carrier to a patient topically.
108 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zerom, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
109 . The method of claim 108 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
110 . The method of claim 108 , including administering said compound incorporated in said carrier to a patient parenterally.
111 . The method of claim 108 , including administering said compound incorporated in said carrier to a patient orally.
112 . The method of claim 108 , including administering said compound incorporated in said carrier to a patient topically.
113 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein A is selected from the group consisting of CH and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero, and R 3 is zero when A is zero;
wherein R 4 is selected from the group ,consisting of hydrogen and lower alkyl group; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons.
114 . The compound, and pharmaceutically acceptable salts thereof, of claim 113 , wherein said lower alkyl groups are branched, unbranched and alicyclic; said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; wherein said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; wherein said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl groups; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of-methyl; ethyl, n-propyl,-n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy group, chlorine atom, bromine atom and fluorine atom.
115 . The compound, and pharmaceutically acceptable salts thereof, of claim 113 , wherein X is NH 2 , Y is NH 2 A is zero, B is CH, R 1 is hydrogen, R 3 is zero, R 4 is hydrogen, R 5 is selected from the group consisting of hydrogen and methyl and R 2 is selected from the group consisting of benzyl, 3,4,5 trimethoxybenzyl, 3,5-dimethoxybenzyl, 2,5-dimethoxybenzyl, 3,4-dichlorobenzyl, 2,4-dichlorobenzyl, 2,6-dichlorobenzyl, 2-CH 2 -naphthyl, C 4 H 4 benzyl, and 4-benzoyl-L-glutamate.
116 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
117 . The method of claim 116 , wherein said illness is cancer.
118 . The method of claim 116 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
119 . The method of claim 116 , wherein said carrier is selected from the-group consisting of physiologic saline and 5% dextrose for injection.
120 . The method of claim 116 , including administering said compound incorporated in said carrier to a patient parenterally.
121 . The method of claim 116 , including administering said compound incorporated in said carrier to a patient orally.
122 . The method of claim 116 , including administering said compound incorporated in said carrier to a patient topically.
123 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group,-p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and lower alkyl group; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
124 . The method of claim 123 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
125 . The method of claim 123 , including administering said compound incorporated in said carrier to a patient parenterally.
126 . The method of claim 123 , including administering said compound incorporated in said carrier to a patient orally.
127 . The method of claim 123 , including administering said compound incorporated in said carrier to a patient topically.
128 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ;
wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond;
wherein Z 4 , Z 5 and Z 6 are different and are selected from the group consisting of R 4 , R 5 and
wherein A is selected from the group consisting of CH, sulfur and zero;
wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero;
wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero;
wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl, group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero;
wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero;
wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group;
wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group;
where R 4 is the same or different than R 5 ;
wherein each of said R 4 , R 5 and
substituents is used once; and
wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons.
129 . The compound, and pharmaceutically acceptable salts thereof, of claim 128 , wherein said lower alkyl groups are branched, unbranched and alicyclic; said alkylaryl group is selected from the group consisting of an alkylphenyl and alkylbenzyl group; wherein said alkyldiaryl group is selected from the group consisting of alkylnaphthyl, alkylbenzothiophene, alkylindene, alkylbenzofuran, alkylindole, and alkylaminoquinoline; wherein said alkyltriaryl group is an alkylanthracyl group; wherein said substituted aryl group, diaryl group and triaryl group is selected from the group consisting of a mono-, di- and tri-substituted aryl group, diaryl group and triaryl group; wherein said substituted alkylaryl group is selected from the group consisting of mono-, di- and tri-substituted alkylphenyl and alkylbenzyl group; wherein each substituted alkyldiaryl and alkyltriaryl group is selected from the group consisting of a mono-, di- and tri-substituted alkylnaphthyl, alkylbenzothiophene, alkylindole, alkylbenzofuran, alkylindine, alkylaminoquinoline and alkylanthracyl group; and wherein each substituent is the same or different and is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy group, chlorine atom, bromine atom and fluorine atom.
130 . The compound, and pharmaceutically acceptable salts thereof, of claim 128 , wherein X is NH 2 , Y is NH 2 , the bond between L and M is a single bond, A is sulfur, R 3 is zero, B is CH, R 1 is hydrogen and R 2 is phenyl.
131 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 4 , Z 5 and Z 6 are different and are selected from the group consisting of R 4 , R 5 and wherein A is selected from the group consisting of CH, sulfur and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group,:an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 4 is the same or different than R 5 ; wherein each of said R 4 , R 5 and substituents is used once; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
132 . The method of claim 131 , wherein said illness is cancer.
133 . The method of claim 131 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
134 . The method of claim 131 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
135 . The method of claim 131 , including administering said compound incorporated in said carrier to a patient parenterally.
136 . The method of claim 131 , including administering said compound incorporated in said carrier to a patient orally.
137 . The method of claim 131 , including administering said compound incorporated in said carrier to a patient topically.
138 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z 4 , Z 5 and Z 6 are different and are selected from the group consisting of R 4 , R 5 and wherein A is selected from the group consisting of CH, sulfur and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero, and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, or alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group and zero, and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 5 is selected from the group consisting of hydrogen and a lower alkyl group; wherein R 4 is the same or different than R 5 ; wherein each of said R 4 , R 5 and substituents is used once; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
139 . The method of claim 138 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
140 . The method of claim 138 , including administering said compound incorporated in said carrier to a patient parenterally.
141 . The method of claim 138 , including administering said compound incorporated in said carrier to a patient orally.
142 . The method of claim 138 , including administering said compound incorporated in said carrier to a patient topically.
143 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, an pharmaceutically acceptable salts thereof, having the formula: wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen, wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
144 . The method of claim 143 , wherein said illness is cancer.
145 . The method of claim 143 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
146 . The method of claim 143 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
147 . The method of claim 143 , including administering said compound incorporated in said carrier to a patient parenterally.
148 . The method of claim 143 , including administering said compound incorporated in said carrier to a patient orally.
149 . The method of claim 143 , including administering said compound incorporated in said carrier to a patient topically.
150 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen, wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from about 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering,a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
151 . The method of claim 150 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
152 . The method of claim 150 , including administering said compound incorporated in said carrier to a patient parenterally.
153 . The method of claim 150 , including administering said compound incorporated in said carrier to a patient orally.
154 . The method of claim 150 , including administering said compound incorporated in said carrier to a patient topically.
155 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero, but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl and p-aroyl-L-glutamate; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
156 . The method of claim 155 , wherein said illness is cancer.
157 . The method of claim 155 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
158 . The method of claim 155 , wherein X and Y are both NH 2 , A is CH, B is sulfur, R 1 is zero, R 2 is 2-naphthyl, R 3 is hydrogen and R 4 is hydrogen.
159 . The method of claim 155 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
160 . The method of claim 155 , including administering said compound incorporated in said carrier to a patient parenterally.
161 . The method of claim 155 , including administering said compound incorporated in said carrier to a patient orally.
162 . The method of claim 155 , including administering said compound incorporated in said carrier to a patient topically.
163 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein X and Y are the same or different and are selected from the group consisting of OH and NH 2 ; wherein L and M are selected from the group consisting of carbon and CH, the chemical bond between L and M is selected from the group consisting of a single bond and a double bond, L and M are carbon when the bond is a double bond, and L and M are CH when the bond is a single bond; wherein Z and Z 1 are different and are selected from the group consisting of R 4 and where Z is R 4 when Z 1 is and Z is when Z 1 is R 4 ; wherein A is selected from the group consisting of CH and zero; wherein B is selected from the group consisting of sulfur, nitrogen, oxygen, CH, N—CH 2 , CH 2 —N, CH 2 —CH 2 , and zero; wherein R 1 is selected from the group consisting of hydrogen, a lower alkyl group, a nitroso group, a formyl group and zero and R 1 is zero when B is sulfur, oxygen or zero; wherein R 2 is selected from the group consisting of a lower alkyl group, p-aroyl-L-glutamate, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, an alkoxyaryloxy group, a halogen and zero, but R 2 is not 3,4,5-trimethoxyphenyl, 3,4,5-trichlorophenyl, 3,4-dichlorophenyl, 2,5-dimethoxyphenyl or p-benzoyl-L-glutamate when R 1 is hydrogen and R 4 is hydrogen, and R 2 is not p-benzoyl-L-glutamate when R 1 is methyl; wherein R 3 is selected from the group consisting of hydrogen, a lower alkyl group, and zero and R 3 is zero when A is zero; wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl group and S—R 7 where R 7 is selected from the group consisting-of phenyl, mono-, di-,and tri-substituted phenyl, naphthyl, mono-, di- and tri-substituted naphthyl, and p-aroyl-L-glutamate; and wherein each lower alkyl group is independently selected from the group consisting of lower alkyl groups having from 1 to 6 carbons; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
164 . The method of claim 163 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
165 . The method of claim 163 , including administering said compound incorporated in said carrier to a patient parenterally.
166 . The method of claim 163 , including administering said compound incorporated in said carrier to a patient orally.
167 . The method of claim 163 , including administering said compound incorporated in said carrier to a patient topically.
168 . A method of synthesizing pyrrolo-[2,3-d]pyrimidine compounds, and pharmaceutically acceptable salts thereof, having the formula:
wherein Q is selected from the group consisting of nitrogen and sulfur;
wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen;
wherein R 10 is selected from the group consisting of hydrogen and a lower alkyl group; and
wherein R 10 is a lower alkyl when Q is nitrogen, comprising the steps of:
a) debrominating a pyrrole;
b) fusing the product of step a) with an amide;
c) condensing the product of step b) with a nucleophile;
d) reducing the product of step c); and
e) purifying the compounds of step d).
169 . The method of claim 168 , wherein the nucleophile of step c) is a compound having the general structure
wherein Q is selected from the group consisting of nitrogen and sulfur;
wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen;
wherein R 10 is selected from the group consisting of hydrogen and a lower alkyl group; and
wherein R 10 is a lower alkyl when Q is nitrogen.
170 . A compound, and pharmaceutically acceptable salts thereof, having the formula:
wherein Q is selected from the group consisting of nitrogen and sulfur;
wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen;
wherein R 10 is selected from the group consisting of hydrogen and a lower alkyl group; and
wherein R 10 is a lower alkyl when Q is nitrogen.
171 . A method of therapeutically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein Q is selected from the group consisting of nitrogen and sulfur; wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen; wherein R 10 is selected from the group consisting of hydrogen and a lower alkyl group; and wherein R 10 is a lower alkyl when Q is nitrogen; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a therapeutically effective amount of said compound incorporated in said carrier to a patient.
172 . The method of claim 171 , wherein said illness is cancer.
173 . The method of claim 171 , wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
174 . The method of claim 171 , wherein X and Y are both NH 2 , A is CH, B is sulfur, R 1 is zero, R 2 is,2-naphthyl, R 3 is hydrogen and R 4 is hydrogen.
175 . The method of claim 171 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
176 . The method of claim 171 , including administering said compound incorporated in said carrier to a patient parenterally.
177 . The method of claim 171 , including administering said compound incorporated in said carrier to a patient orally.
178 . The method of claim 171 , including administering said compound incorporated in said carrier to a patient topically.
179 . A method of prophylactically treating a patient for an illness comprising the steps of:
a) employing a compound, or pharmaceutically acceptable salts thereof, having the formula: wherein Q is selected from the group consisting of nitrogen and sulfur; wherein R is selected from the group consisting of a lower alkyl group, a p-aroyl-L-glutamate group, an aryl group, an alkylaryl group, a substituted aryl group, a substituted alkylaryl group, a diaryl group, a triaryl group, an alkyldiaryl group, an alicyclic hydrocarbon group, an alkyltriaryl group, a substituted diaryl group, and a substituted triaryl group, and each substituent of the substituted aryl group, diaryl group, triaryl group, or the substituted alkylaryl group, alkyldiaryl group, alkyltriaryl group is the same or different and is selected from the group consisting of a lower alkyl group, an alkoxy, a substituted alkoxyaryloxy group and a halogen; wherein R 10 is selected from the group consisting of hydrogen and a lower alkyl group; and wherein R 10 is a lower alkyl when Q is nitrogen; b) incorporating said compound in a suitable pharmaceutical carrier; and c) administering a prophylactically effective amount of said compound incorporated in said carrier to a patient; wherein said illness is selected from the group consisting of infection caused by Pneumocystis carinii and Toxoplasmosis gondii.
180 . The method of claim 179 , wherein said carrier is selected from the group consisting of physiologic saline and 5% dextrose for injection.
181 . The method of claim 179 , including administering said compound incorporated in said carrier to a patient parenterally.
182 . The method of claim 179 , including administering said compound incorporated in said carrier to a patient orally.
183 . The method of claim 179 , including administering said compound incorporated in said carrier to a patient topically.Join the waitlist — get patent alerts
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