Pyrido(3,2-d)pyrimidines and pharmaceutical compositions useful for medical treatment

A pyrido(3,2-d)pyrimidine derivative having the general formula:

• wherein:
• R1 is selected from the group consisting of hydrogen, halogen, C1-7 alkyl, aryl, amino, acetamido, N-protected amino, (mono- or di) C1-7 alkylamino, (mono- or di) C1-4 alkyl-arylamino, C1-7 alkyloxy, and groups of the formula R6—NR7R12, wherein R6 is a bond or C1-3 alkylene, wherein R7 and R12 together form a heterocycle,
• R2 is selected from the group consisting of (mono- or di-) C1-12 alkylamino;
• monoarylamino;
• diarylamino;
• (mono- or di-) C1-4 alkylarylamino;
• (mono- or di-) arylC1-4 alkylamino;
• morpholinyl;
• mercapto C1-7 alkyl;
• C1-7 alkoxy;
• homopiperazinyl and piperazinyl, wherein said homopiperazinyl or piperazinyl is optionally N-substituted, with a substituent R5 selected from the group consisting of acyl, heterocyclic-substituted alkyl, heterocyclic, aryloxyalkyl, arylalkyl and aryl, wherein the aryl moiety of each of said arylalkenyl, aryloxyalkyl, arylalkyl and aryl radicals is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-7 alkyl;
• R3 and R4 are independently selected from the group consisting of hydrogen, heteroaryl and aryl groups, wherein said heteroaryl or aryl groups are optionally substituted with one or more substituents selected from the group consisting of halogen, C1-7 alkyl, hydroxyl, C1-7 alkoxy, C3-10 cycloalkoxy,
• or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof, or an N-oxide thereof, or a solvate thereof.

A pyrido[3,2-d]pyrimidine derivative selected from the group consisting of:

• 2-chloro-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-dimethylamino-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-[(N-hydroxyethyl)morpholino]-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-(1-methyl-2-pyrrolidino-ethoxy)-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-(2-phenoxyethoxy)-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-phenyl-4-(4-[3-methylphenyl)amino]carbonyl]piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[4-(ethoxycarbonyl)piperidin-1-yl]-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-[3,4-(methylenedioxy)aniline]-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(N-methyl-piperazino)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-(thienyl-2-methylamino)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine-2,4-diamine
• 2-amino-4-[4-(2-aminoethyl)morpholino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(aminomethyl)pyridino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2,4-diamino-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(4-{[(3-methylphenyl)amino]carbonyl}piperazin-1-yl)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(piperazin-1-yl)-acetic acid N-(2-thiazolyl)-amide]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-morpholino-4-[(N-3-methyl-phenylcarbamoyl-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-butoxy-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-methoxy-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxy-phenyl)-pyrido[3,2-d]pyrimidine
• 2-(p-tolylamino)-4-[(N-3-methylphenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxy-phenyl)-pyrido[3,2-d]pyrimidine
• 2-[(3-chloro-4-fluoro-anilino)-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2,4-diamino-6-(4-hydroxy-3-methoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2,4-diamino-6-(3-chloro-4-methoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(N-4-fluoro-phenyl-carbamoyl)-piperazin-1-yl]-6-(4-hydroxy-3-methoxyphenyl)-pyrido[3,2-d]pyrimidine
• 4-(4-methyl-phenyl-piperazin-1-yl)-6-(3,4-dimethoxy-phenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(N-piperazin-1-yl)-6-(1,4-benzodioxane-phenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(morpholino)-6-(1,4-benzodioxane-phenyl)pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3,4-dichloro-phenyl)pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(1,4-benzodioxane)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3,4-methylenedioxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(N-4-chloro-benzylcarbamoyl)-piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(piperazin-1-yl acetic acid N-(2-thiazolyl)-amide)]-6-3,4-methylenedioxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[N-(3-methyl-phenyl-carbamoyl)-piperazin-1-yl]-6-(3,4-methylenedioxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[N-(3-methyl-phenyl-carbamoyl)-piperazin-1-yl]-6-(3,4-dichlorophenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[N-(3-methyl-phenyl-carbamoyl)-piperazin-1-yl]-6-(1,4-benzodioxane)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(piperazin-1-yl acetic acid N-(2-thiazolyl)-amide]-6-(1,4-benzodioxane)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(piperazin-1-yl acetic acid N-(2-thiazolyl)-amide]-6-(3,4-dichlorophenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-[(S)-3-(Boc-amino)pyrrolidine]-6-chloro-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(S)-3-(Boc-amino)pyrrolidine]-6-chloro-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(S)-3-(Boc-amino)pyrrolidine]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(S)-3-(amino)pyrrolidine]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[3-(S)-4-chloro-phenoxy-acetyl-amino)-pyrrolidin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[3-(S)-3-methyl phenyl carbamoyl pyrrolidin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-[(R)-3-Boc-aminopyrrolidin-1-yl]-6-chloro pyrido[3,2-d]pyrimidine
• 2-amino-4-[(R)-3-Boc-aminopyrrolidin-1-yl)]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(1-Boc-piperidin-4-yl)amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(1-Boc-piperidin-3-yl)amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(1-Cbz-piperidin-3-yl)amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(R)-3-aminopyrrolidin-1-yl]-6-(3,4-dimethoxy-phenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[3-(R)-(3-methylphenylcarbamoyl)-pyrrolidin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(3-methylphenylcarbamoyl)-ethylenediamine-1-N-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(3-methylphenylcarbamoyl)-3-aminopropane-amino-1-N-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[1-(3-methylphenylcarbamoyl)piperidin-4-yl)amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(3-methylphenylcarbamoyl)piperidin-3-yl)amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-(4-chlorophenoxy-acetyl-ethylenediamine-1-N-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[3-N-(4-chlorophenoxy-acetyl)-3-amino-propane-amine-1-N-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(3-(R)-(4-chlorophenoxyacetyl-amino)-pyrrolidin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[(3-carboxylic acid isobutylamide)-piperidin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-(4-chlorophenyl-4-hydroxypiperidin-1-yl)-6-(3,4-dimethoxy-phenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[4-(N-2-phenylethylacetamid-2-yl)piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[3-(4-acetylpiperazin-1-yl)-propan-3-one-1-yl-amino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-(N-pyrrolidinyl-acetamid-2-yl-piperazin-1-yl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(N-pyridinylacetamid-2-yl-piperazin-1-yl)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[N-(piperazino)-acetyl-morpholino]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-[2-amino-1-(4-methyl-piperazin-1-yl)-ethanone]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-[(N-pyridin-3-yl-acetamid)-2-yl-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-[(N-methyl-N-phenylacetamid)-2-yl-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine
• 2-acetamido-4-benzyloxy-6-chloro-pyrido[3,2-d]pyrimidine
• 2-amino-4-benzyloxy-6-(o-fluorophenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-benzyloxy-6-(m-fluorophenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-benzyloxy-6-(p-fluorophenyl)-pyrido[3,2-d]pyrimidine
• 2-amino-4-(1,8-diaminooctyl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(1,9-diaminononyl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(1,10-diaminodecyl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-amino-4-(1,12-diaminododecyl)-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3-methyl-4-methoxyphenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3-chloro-4-methoxy-phenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3-chloro-4-ethoxy-phenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3-fluoro-4-ethoxy-phenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3-methyl-4-fluoro-phenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3,4-dichloro-phenyl)pyrido-[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(3,4-(methylenedioxy)phenyl)pyrido[3,2-d]pyrimidine
• 2-acetamido-4-(1,2,4-triazolyl)-6-(1,4-benzodioxane-phenyl)pyrido[3,2-d]pyrimidin-4(3H)-one

A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a pyrido(3,2-d)pyrimidine derivative having the general formula:

• wherein:
• R1 is selected from the group consisting of hydrogen, halogen, cyano, carboxylic acid, acyl, thioacyl, alkoxycarbonyl, acyloxy, carbonate, carbamate, C1-7 alkyl, aryl, amino, acetamido, N-protected amino, (mono- or di) C1-7 alkylamino, (mono- or di) arylamino, (mono- or di) C3-10 cycloalkylamino, (mono- or di) hydroxy C1-7 alkylamino, (mono- or di) C1-4 alkyl-arylamino, mercapto C1-7 alkyl, C1-7 alkyloxy, and groups of the formula R6—NR7R12, wherein R6 is a bond or C1-3 alkylene, wherein R7 and R12 are independently selected from the group consisting of hydrogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, aryl, arylalkyl, C3-10 cycloalkyl and heteroaryl, or wherein R7 and R12 together form a heterocycle,
• R2 is selected from the group consisting of (mono- or di-) C1-12 alkylamino;
• monoarylamino;
• diarylamino;
• (mono- or di-) C3-10 cycloalkylamino;
• (mono- or di-) hydroxyC1-7 alkylamino;
• (mono- or di-) C1-4 alkylarylamino;
• (mono- or di-) arylC1-4 alkylamino;
• morpholinyl;
• mercapto C1-7 alkyl;
• C1-7 alkoxy, homopiperazinyl and piperazinyl, wherein said homopiperazinyl or piperazinyl is optionally N-substituted with a substituent R5 selected from the group consisting of formyl, acyl, thioacyl, amide, thioamide, sulfonyl, sulfinyl, carboxylate, thiocarboxylate, amino-substituted acyl, alkoxyalkyl, C3-10 cycloalkyl-alkyl, C3-10 cycloalkyl, dialkylaminoalkyl, heterocyclic-substituted alkyl, acyl-substituted alkyl, thioacyl-substituted alkyl, amido-substituted alkyl, thioamido-substituted alkyl, carboxylato-substituted alkyl, thiocarboxylato-substituted alkyl, (amino-substituted acyl)alkyl, heterocyclic, carboxylic acid ester, w-cyanoalkyl, w-carboxylic ester-alkyl, halo C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, arylalkenyl, aryloxyalkyl, arylalkyl and aryl, wherein the aryl moiety of each of said arylalkenyl, aryloxyalkyl, arylalkyl and aryl radicals is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, halo C1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C1-7 alkoxy, C3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C1-7 alkyl, thio C3-10 cycloalkyl, thioaryl, thio-heterocyclic, arylalkylthio, heterocyclic-substituted alkylthio, formyl, carbamoyl, thiocarbamoyl, ureido, thioureido, sulfonamido, hydroxylamino, alkoxy-amino, mercaptoamino, thioalkylamino, acylamino, thioacylamino, cyano, carboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, thiocarboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, alkylamino, cycloalkylamino, alkenylamino, cycloalkenylamino, alkynylamino, arylamino, arylalkylamino, hydroxyalkylamino, mercaptoalkylamino, heterocyclic amino, hydrazino, alkylhydrazino and phenylhydrazino;
• R3 and R4 are independently selected from the group consisting of hydrogen, heteroaryl and aryl groups, wherein said heteroaryl or aryl groups are optionally substituted with one or more substituents selected from the group consisting of halogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, halo C1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C1-7 alkoxy, C3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C1-7 alkyl, thio C3-10 cycloalkyl, thioaryl, thio-heterocyclic, arylalkylthio, heterocyclic-substituted alkylthio, formyl, carbamoyl, thiocarbamoyl, ureido, thioureido, sulfonamido, hydroxylamino, alkoxy-amino, mercaptoamino, thioalkylamino, acylamino, thioacylamino, cyano, carboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, thiocarboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, alkylamino, cycloalkylamino, alkenylamino, cyclo-alkenylamino, alkynylamino, arylamino, arylalkylamino, hydroxyalkylamino, mercaptoalkylamino, heterocyclic amino, hydrazino, alkylhydrazino and phenylhydrazino, provided that R3 and R4 are not both hydrogen, and further provided that R4 is hydrogen when R2 is monoarylamino,
• or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof, or an N-oxide thereof, or a solvate thereof.

A pyrido(3,2-d)pyrimidine derivative represented by the structural formula (II)

• or the structural formula (III)
• or the structural formula (IV)
• wherein:
• R1 is selected from the group consisting of hydrogen, halogen, cyano, carboxylic acid, acyl, thioacyl, alkoxycarbonyl, acyloxy, carbonate, carbamate, C1-7 alkyl, aryl, amino, acetamido, N-protected amino, (mono- or di) C1-7 alkylamino, (mono- or di) arylamino, (mono- or di) C3-10 cycloalkylamino, (mono- or di) hydroxy C1-7 alkylamino, (mono- or di) C1-4 alkyl-arylamino, mercapto C1-7 alkyl, C1-7 alkyloxy, and groups of the formula R6—NR7R12, wherein R6 is a bond or C1-3 alkylene, wherein R7 and R12 are independently selected from the group consisting of hydrogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, aryl, arylalkyl, C3-10 cycloalkyl and heteroaryl, or wherein R7 and R12 together form a heterocycle;
• R2 is selected from the group consisting of (mono- or di-) C1-12 alkylamino;
• monoarylamino;
• diarylamino;
• (mono- or di-) C3-10 cycloalkylamino;
• (mono- or di-) hydroxyC1-7 alkylamino;
• (mono- or di-) C1-4 alkylarylamino;
• (mono- or di-) arylC1-4 alkylamino;
• morpholinyl;
• mercapto C1-7 alkyl;
• C1-7 alkoxy, homopiperazinyl and piperazinyl, wherein said homopiperazinyl or piperazinyl is optionally N-substituted with a substituent R5
• R5 is selected from the group consisting of formyl, acyl, thioacyl, amide, thioamide, sulfonyl, sulfinyl, carboxylate, thiocarboxylate, amino-substituted acyl, alkoxyalkyl, C3-10 cycloalkyl-alkyl, C3-10 cycloalkyl, dialkylaminoalkyl, heterocyclic-substituted alkyl, acyl-substituted alkyl, thioacyl-substituted alkyl, amido-substituted alkyl, thioamido-substituted alkyl, carboxylato-substituted alkyl, thiocarboxylato-substituted alkyl, (amino-substituted acyl)alkyl, heterocyclic, carboxylic acid ester, ω-cyanoalkyl, ω-carboxylic ester-alkyl, halo C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, arylalkenyl, aryloxyalkyl, arylalkyl and aryl, wherein the aryl moiety of each of said arylalkenyl, aryloxyalkyl, arylalkyl and aryl radicals is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, halo C1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C1-7 alkoxy, C3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C1-7 alkyl, thio C3-10 cycloalkyl, thioaryl, thio-heterocyclic, arylalkylthio, heterocyclic-substituted alkylthio, formyl, carbamoyl, thiocarbamoyl, ureido, thioureido, sulfonamido, hydroxylamino, alkoxy-amino, mercaptoamino, thioalkylamino, acylamino, thioacylamino, cyano, carboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, thiocarboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, alkylamino, cycloalkylamino, alkenylamino, cyclo-alkenylamino, alkynylamino, arylamino, arylalkylamino, hydroxyalkylamino, mercaptoalkylamino, heterocyclic amino, hydrazino, alkylhydrazino and phenylhydrazino;
• R3 is independently selected from the group consisting of hydrogen, heteroaryl and aryl groups, wherein said heteroaryl or aryl groups are optionally substituted with one or more substituents selected from the group consisting of halogen, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, halo C1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C1-7 alkoxy, C3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C1-7 alkyl, thio C3-10 cycloalkyl, thioaryl, thio-heterocyclic, arylalkylthio, heterocyclic-substituted alkylthio, formyl, carbamoyl, thiocarbamoyl, ureido, thioureido, sulfonamido, hydroxylamino, alkoxy-amino, mercaptoamino, thioalkylamino, acylamino, thioacylamino, cyano, carboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, thiocarboxylic acid or esters or thioesters or halides or anhydrides or amides thereof, alkylamino, cycloalkylamino, alkenylamino, cyclo-alkenylamino, alkynylamino, arylamino, arylalkylamino, hydroxyalkylamino, mercaptoalkylamino, heterocyclic amino, hydrazino, alkylhydrazino and phenylhydrazino;
• R2′ is selected from the group consisting of:
• piperazinyl or homopiperazinyl wherein one or more carbon atoms of said piperazinyl or homopiperazinyl are independently substituted with C1-4 alkyl, or two carbon atoms of said piperazinyl or homopiperazinyl together with their alkyl substituent form a C1-4 alkylene group, and wherein said piperazinyl or homopiperazinyl is optionally N-substituted with R5;
• piperidin-4-yl-amino, piperidin-3-yl-amino, piperidin-4-yl-oxy, pyrrolidin-1-yl, 3-amino-pyrrolidin-1-yl, pyrrolidin-3-yl-amino or 2,6-diazabicyclo[3.2.0]heptan-2-yl, wherein said piperidin-4-yl, piperidin-3-yl, 3-amino-pyrrolidin-1-yl, pyrrolin-3-yl or 2,6-diazabicyclo[3.2.0]heptan-2-yl is optionally N-substituted with R5 or C1-4alkylarylcarbamoyl;
• or wherein any carbon atom of said piperidin-1-yl may be further substituted with one or more substituent selected from the group consisting of hydroxy, aryl, C1-4alkylcarbamoyl, C1-4alkoxycarbonyl and C1-4alkylarylcarbamoyl;
• piperazinyl or homopiperazinyl being N-substituted with a substituent selected from the group consisting of C1-4alkyl;
• arylcarbamoyl-substituted alkanoyl;
• arylalkanoyl wherein alkanoyl is substituted with one or more substituents selected from the group consisting of amino, hydroxy and halogen;
• mono-C1-4alkylaryl-carbamoyl;
• di-C1-4alkylaryl-carbamoyl;
• tri-C1-4alkylaryl-carbamoyl;
• mono-C1-4alkylaryl-C1-4alkylcarbamoyl;
• di-C1-4alkylaryl-C1-4alkylcarbamoyl;
• tri-C1-4alkylaryl-C1-4alkylcarbamoyl;
• alkoxycarbonyl;
• alkanoyl substituted with one or more substituents independently selected from the group consisting of amino, alkoxycarbonyl, alkylcarbamate, arylamido and arylcarbamoyl;
• arylalkanoyl substituted by alkylcarbamate;
• cycloalkylcarbamoyl;
• alkoxyalkanoyl;
• dialkyl-carbamoyl;
• heterocyclic carbamoyl C1-4alkyl;
• arylC1-4alkylcarbamoyl;
• heterocyclic carbonyl C1-4alkyl and aryl C1-4alkylcarbamoyl C1-4alkyl;
• triazolyl;
• heterocyclic amino;
• heterocyclic C1-4alkylamino;
• alkoxy C1-4alkylamino;
• amino cycloalkylamino;
• amino C2-14alkylamino;
• amino C1-6alkylamino wherein the N-atom is further substituted with C1-4alkylarylcarbamoyl or aryloxy C1-4alkanoyl;
• aryl C1-4alkoxy;
• 3-amino-pyrrolidin-1-yl;
• N—C1-4alkyl-N-arylcarbamoyl;
• and;
• C1-4alkyl or alkanoyl substituted heterocyclic carbonyl C1-4alkylamino;
• and,
• R3′ is an aryl group substituted with one or more substituents selected from the group consisting of heterocyclic;
• C3-10 cycloalkylcarbamoyl;
• C1-4 alkylcarbamoyl;
• C1-4 alkylsulfonyl;
• C1-4 alkylsulfonamido;
• C1-4 alkyl-carboxylate;
• C1-4 alkyl and C1-4 alkoxy substituted with one or more substituents selected from the group consisting of amino, halogen, cyano and C1-4alkoxy;
• or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof, or an N-oxide thereof, or a solvate thereof.