Human immunodeficiency virus protease inhibitors

A composition for inhibiting HIV protease, the composition comprising a compound of formula

• wherein R, R1, R2, R3, R4, R5 and R6 each independently are:
• R═H, an alkyl, wherein the alkyl is a straight or branched hydrocarbon chain having from 1 to 25 of carbon atoms, an aryl, wherein the aryl is a substituted benzene ring, system fused to one or more substituted benzene ring an aryl alkyl, a heterocycle, wherein the heterocycle is a three to twelve-membered heterocyclic ring optionally possessing one or more degrees of unsaturation, and containing one or more heteroatomic substitutions selected from the group consisting of —S—, —SO—, —SO2—, —O—, or —N—,
• a substitution of the alkyl, wherein one or more carbon atoms of the straight or branched hydrocarbon chain are substituted with a substituent selected from the group consisting of alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, silyloxy optionally substituted by alkoxy, alkyl, or aryl, silyl optionally substituted by alkoxy, alkyl, or aryl, nitro, cyano, halogen, and perfluoroalkyl;
• a substitution of the aryl, wherein one or more carbon atoms of the one or more substituted benzene ring are substituted with a substituent selected from the group consisting of alkyl, alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, tetrazolyl, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, acyl, aroyl, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, silyloxy optionally substituted by alkoxy, alkyl, or aryl, silyl optionally substituted by alkoxy, alkyl, or aryl, nitro, cyano, halogen, and perfluoroalkyl;
• and
• a substitution of the heterocycle, wherein one or more carbon atoms of the heterocyclic ring are substituted with a substituent selected from the group consisting of alkyl, alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, nitro, cyano, halogen, and perfluoroalkyl;
• where R7═H, an electron donating group, or an electron withdrawing group at some or all the positions on the aromatic ring;
• R2, R3, R4, and R5 are each independently H, an electron donating group, or an electron withdrawing group at some or all the positions on the aromatic ring,
• wherein the electron donating group is selected from the group consisting of an alkyl group, an alcohol group, an alkoxy group, an amino group, and a phenolic group, and
• wherein the electron withdrawing group is selected from the group consisting of a halogen, a nitrile, a carboxylic acid, a carbonyl, a carboxylic group, and an aldehyde;
• R6 is H, a phosphate or amino acid ester(s) or salt(s) thereof;
• wherein “*” represents a chiral center, and
• a pharmaceutically acceptable carrier.

A method for inhibiting a HIV protease in a subject, the method comprising steps:

• (a) administering to a subject in need thereof a pharmaceutical composition comprising
• (i) a therapeutically effective amount of a compound of formula:
• wherein R, R1, R2, R3, R4, R5 and R6 each independently are:
• R═H, an alkyl, wherein the alkyl is a straight or branched hydrocarbon chain having from 1 to 25 of carbon atoms, an aryl, wherein the aryl is a substituted benzene ring system fused to one or more substituted benzene ring;
• an aryl alkyl, a heterocycle, wherein the heterocycle is a three to twelve-membered heterocyclic ring optionally possessing one or more degrees of unsaturation, and containing one or more heteroatomic substitutions selected from the group consisting of —S—, —SO—, —SO2—, —O—, or —N—,
• a substitution of the alkyl, wherein one or more carbon atoms of the straight or branched hydrocarbon chain are substituted with a substituent selected from the group consisting of alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, silyloxy optionally substituted by alkoxy, alkyl, or aryl, silyl optionally substituted by alkoxy, alkyl, or aryl, nitro, cyano, halogen, and perfluoroalkyl;
• a substitution of the aryl, wherein one or more carbon atoms of the one or more substituted benzene ring are substituted with a substituent selected from the group consisting of alkyl, alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, tetrazolyl, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, acyl, aroyl, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, silyloxy optionally substituted by alkoxy, alkyl, or aryl, silyl optionally substituted by alkoxy, alkyl, or aryl, nitro, cyano, halogen, and perfluoroalkyl;
• and
• a substitution of the heterocycle, wherein one or more carbon atoms of the heterocyclic ring are substituted with a substituent selected from the group consisting of alkyl, alkoxy, alkylsulfanyl, alkylsulfenyl, alkylsulfonyl, oxo, hydroxy, mercapto, amino optionally substituted by alkyl, carboxy, carbamoyl optionally substituted by alkyl, aminosulfonyl optionally substituted by alkyl, nitro, cyano, halogen, and perfluoroalkyl;
• where R7═H, an electron donating group, or an electron withdrawing group at some or all the positions on the aromatic ring;
• R2, R3, R4, and R5 are each independently H, an electron donating group, or an electron withdrawing group at some or all the positions on the aromatic ring;
• wherein the electron donating group is selected from the group consisting of an alkyl group, an alcohol group, an alkoxy group, an amino group, trifluoromethoxy, difluoromethoxy, amide, substituted amide, urea, substituted urea, sulphonamide, substituted sulphonamide, and a phenolic group, and
• wherein the electron withdrawing group is selected from the group consisting of a halogen, a nitrile, a carboxylic acid, a carbonyl, a carboxylic group, a nitro group, trifluoromethyl, difluoromethyl, nitro, sulphone, sulphonamide, amide, N-substituted amide, and an aldehyde;
• R6 is H, a phosphate or amino acid ester(s) or salt(s) thereof;
• wherein “*” represents a chiral center, and
• (ii) a pharmaceutically acceptable carrier;
• thereby reducing the enzymatic activity of a HIV protease.