PYRIDO(3,2-D)PYRIMIDINES AND PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING HEPATITIS C

• US 20090131414A1
• Filed: 06/26/2006
• Published: 05/21/2009
• Est. Priority Date: 06/24/2005
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Lee, William A., Herdewijn, Piet Andre Maurits Maria, De Jonghe, Steven Cesar Alfons, Watkins, William John
• Granted Patent: US 8,232,278 B2
• Time in Patent Office: Days
• US Class Current: 514/218
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Specifically substituted pyrido(3,2-d)pyrimidine derivatives having the structural formula (I) are useful for the treatment of hepatitis C.

Claims

1-19. -19. (canceled)

20. A method of treatment or prevention of an infection due to a virus from the Flaviridae family comprising the step of administering a patient in need thereof of a therapeutic amount of a pyrido(3,2-d)pyrimidine derivative having the structural formula:

wherein;

R₁ is selected from the group consisting of hydrogen, halogen, cyano, carboxylic acid, acyl, thioacyl, alkoxycarbonyl, acyloxy, carbonate, carbamate, C_1-7 alkyl, aryl, amino, acetamido, N-protected amino, (mono- or di) C_1-7 alkylamino, (mono- or di) arylamino, (mono- or di) C_3-10 cycloalkylamino, (mono- or di) hydroxy C_1-7 alkylamino, (mono- or di) C_1-4 alkyl-arylamino, mercapto C_1-7 alkyl, C_1-7 alkyloxy, and groups of the formula R₆—

NR₇R₁₂, wherein R₆ is a bond or C_1-3 alkylene, wherein R₇ and R₁₂ are independently selected from the group consisting of hydrogen, C_1-7 alkyl, C_2-7 alkenyl, C_2-7 alkynyl, aryl, arylalkyl, C_3-10 cycloalkyl and heteroaryl, or wherein R₇ and R₁₂ together form a heterocycle,

R₂ is selected from the group consisting of (mono- or di-) C_1-12 alkylamino;

monoarylamino;

diarylamino;

(mono- or di-) C_3-10 cycloalkylamino;

(mono- or di-) hydroxyC_1-7 alkylamino;

(mono- or di-) C_1-4 alkylarylamino;

(mono- or di-) arylC_1-4 alkylamino;

morpholinyl;

mercapto C_1-7 alkyl;

C_1-7 alkoxy;

N-containing heterocyclic;

C_1-7 alkoxy-C_1-7 alkoxy;

heterocyclic-substituted C_1-7 alkoxy;

C_3-10 cycloalkoxy;

C_3-10 cycloalkyl-C_1-7 alkoxy;

halo C_1-7 alkyloxy;

aryloxy;

arylalkyloxy;

oxyheterocyclic;

heterocyclic-substituted alkoxy;

thio C_1-7 alkyl-thio C_1-7 alkyl;

heterocyclic-substituted thio C_1-7 alkyl;

thio C_3-10 cycloalkyl;

thio C_3-10 cycloalkyl-C_1-7 alkyl;

halo thio-C_1-7 alkyl;

arylthio;

arylalkylthio;

thioheterocyclic;

heterocyclic-substituted thio C_1-7 alkyl;

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, C_1-7 alkyl, C_3-10 cycloalkyl-alkyl, C_3-10 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, co-cyanoalkyl, co-carboxylic ester-alkyl, halo C_1-7 alkyl, C_2-7 alkenyl, C_2-7 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, C_1-7 alkyl, C_2-7 alkenyl, C_2-7 alkynyl, halo C_1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C_1-7 alkoxy, C_3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C_1-7 alkyl, thio C_3-10 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 and R₄ are independently selected from the group consisting of hydrogen halogen, 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, C_1-7 alkyl, C_2-7 alkenyl, C_2-7 alkynyl, halo C_1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C_1-7 alkoxy, C_3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C_1-7 alkyl, thio C_3-10 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 pharmaceutical acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof or a solvate thereof.

21. The method according to claim 20, wherein said virus belongs to a genus selected from the group consisting of Genus Flavivirus, Genus Hepacivirus and Genus Pestivirus.

22. The method according to claim 20, wherein said infection is hepatitis C.

23. A pyrido(3,2-d)pyrimidine derivative having the structural formula:

wherein;

R₁ is selected from the group consisting of hydrogen, halogen, cyano, carboxylic acid, acyl, thioacyl, alkoxycarbonyl, acyloxy, carbonate, carbamate, C_1-7 alkyl, aryl, amino, acetamido, N-protected amino, (mono- or di) C_1-7 alkylamino, (mono- or di) arylamino, (mono- or di) C_3-10 cycloalkylamino, (mono- or di) hydroxy C_1-7 alkylamino, (mono- or di) C_1-4 alkyl-arylamino, mercapto C_1-7 alkyl, C_1-7 alkyloxy, and groups of the formula R₆—

NR₇R₁₂, wherein R₆ is a bond or C_1-3 alkylene, wherein R₇ and R₁₂ are independently selected from the group consisting of hydrogen, C_1-7 alkyl, C_2-7 alkenyl, C_2-7 alkynyl, aryl, arylalkyl, C_3-10 cycloalkyl and heteroaryl, or wherein R₇ and R₁₂ together form a heterocycle,

R₂ is selected from the group consisting of N-containing heterocyclic;

C_1-7 alkoxy-C_1-7 alkoxy;

heterocyclic-substituted C_1-7 alkoxy;

C_3-10 cycloalkoxy;

C_3-10 cycloalkyl-C_1-7 alkoxy;

halo C_1-7 alkyloxy;

aryloxy;

arylalkyloxy;

oxyheterocyclic;

heterocyclic-substituted alkoxy;

thio C_1-7 alkyl-thio C_1-7 alkyl;

heterocyclic-substituted thio C_1-7 alkyl;

thio C_3-10 cycloalkyl;

thio C_3-10 cycloalkyl-C_1-7 alkyl;

halo thio-C_1-7 alkyl;

arylthio;

arylalkylthio;

thioheterocyclic; and

heterocyclic-substituted thio C_1-7 alkyl;

R₃ and R₄ are independently selected from the group consisting of hydrogen halogen, 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, C_1-7 alkyl, C_2-7 alkenyl, C_2-7 alkynyl, halo C_1-7 alkyl, nitro, hydroxyl, sulfhydryl, amino, C_1-7 alkoxy, C_3-10 cycloalkoxy, aryloxy, arylalkyloxy, oxyheterocyclic, heterocyclic-substituted alkyloxy, thio C_1-7 alkyl, thio C_3-10 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 pharmaceutical acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof or a solvate thereof.

24. A pyrido(3,2-d)pyrimidine derivative according to claim 23, wherein R₁ is not hydrogen.

25. A pyrido(3,2-d)pyrimidine derivative according to claim 23, wherein R₁ is amino or acetamido.

26. A pyrido(3,2-d)pyrimidine derivative according to claim 23, wherein R₁ is amino or acetamido, and further wherein R₃ is a substituted aryl group.

27. A pyrido(3,2-d)pyrimidine derivative according to claim 23, wherein R₁ is amino or acetamido, wherein R₃ is a substituted aryl group and wherein R₄ is hydrogen.

28. A pyrido(3,2-d)pyrimidine derivative according to claim 23, wherein the N-containing heterocyclic of R₁ is selected from the group consisting of N-thiomorpholinyl, N-piperidinyl, N-homopiperidinyl and N-pyrrolidinyl.

30. A method of treatment or prevention of an infection due to a virus from the Flaviridae family comprising the step of administering a patient in need thereof of a therapeutic amount of a pyrido(3,2-d)pyrimidine derivative according to claim 23 or 29.

31. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a pyrido(3,2-d)pyrimidine derivative according to claim 23 or 29.

32. A pharmaceutical composition according to claim 31, further comprising one or more antiviral agents.

33. A pharmaceutical composition according to claim 32, wherein said one or more antiviral agents are selected from the group consisting of retroviral enzyme inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, reverse transcriptase inhibitors and HIV-1 protease inhibitors.

34. A pharmaceutical composition according to claim 32, wherein said one or more antiviral agents are selected from the group consisting of zidovudine, lamivudine, didanosine, stavudine, zalcitabine, nevirapine, delavirdine, foscamet sodium, saquinavir, ritonavir, indinavir, nelfinavir, acemannan, acyclovir, adefovir, alovudine, alvircept, amantadine, aranotin, arildone, atevirdine, pyridine, cidofovir, cipamfylline, cytarabine, desciclovir, disoxaril, edoxudine, enviradene, enviroxime, famciclovir, famotine, fiacitabine, fiaiuridine, floxuridine, fosarilate, fosfonet, ganciclovir, idoxuridine, kethoxal, lobucavir, memotine, methisazone, penciclovir, pirodavir, somantadine, sorivudine, tilorone, trifluridine, valaciclovir, vidarabine, viroxime, zinviroxime, moroxydine, podophyllotoxin, ribavirine, rimantadine, stallimycine, statolon, tromantadine, xenazoic acid, and their pharmaceutically acceptable salts.

35. A pharmaceutical composition according to claim 31, wherein said one or more pharmaceutically acceptable carriers are selected from the group consisting of wetting agents, dispersing agents, stickers, adhesives, surface-active agents, thickening agents, complexing agents, gelling agents, solvents, coatings, antibacterial, antifungal agents and isotonic agents.

36. A pharmaceutical composition according to claim 31, being for oral, rectal, intramuscular or intraperitoneous administration.

29. A pyrido(3,2-d)pyrimidine derivative selected from the group consisting of:

2-acetamido-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine

2-amino-7-chloro-pyrido[3,2-d]pyrimidin-4(3H)one

2-amino-7-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidin-4(3H)one

2-acetamido-7-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidin-4(3H)one

2-acetamido-4-(1,2,4-triazolyl)-7-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-(N-3-methyl-phenyl-carbamoyl)-piperazin-1-1])-7-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-amino-6-phenyl-pyrido[3,2-d]pyrimidin-4(3H)one

2-acetamido-6-phenyl-pyrido[3,2-d]pyrimidin-4(3H)one

2-acetamido-4-(1,2,4-triazolyl)-6-phenyl-pyrido[3,2-d]pyrimidine

2-acetamido-4-(N-piperazin-1-yl)-6-phenyl-pyrido[3,2-d]pyrimidine

2-acetamido-4-(N-morpholino)-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-acetamido-6-chloro-4-(2-ethoxyethoxy)-pyrido[3,2-d]

2-acetamido-6-chloro-4-(2-methoxyethoxy)-pyrido[3,2-d]pyrimidine

2-amino-4-(2-ethoxyethoxy)-6-(2-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-(2-ethoxyethoxy)-6-(3-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-(2-ethoxyethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-(2-methoxyethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-acetamido-4-ethoxy-6-(3,4-dimethoxy)-pyrido[3,2-d]pyrimidine

2-amino-4-trifluoroethoxy-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-ethoxy-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-(methoxy-ethoxy)-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-(isopropoxy)-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-(cyclopropylmethyloxy)-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-(4-morpholino-ethoxy)-6-chloro-pyrido(3,2-d)pyrimidine

2-amino-4-(methoxy-ethoxy)-6-(p-acetamidophenyl)-pyrido(3,2-d)pyrimidine

2-amino-4-(isopropoxy)-6-(p-acetamidophenyl)-pyrido(3,2-d)pyrimidine

2-amino-4-(4-morpholino-ethoxy)-6-(p-acetamidophenyl)-pyrido(3,2-d)pyrimidine

2-amino-4-[N-(4-pentenoyl)piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(2-methylpropionyl)piperazin-1-yl]-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[4-(3,3-dimethylbutyryl)piperazin-1-yl]-6-(3,4-dimethoxyphenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[4-(N-butylcarbamoyl)piperazin-1-yl]-6-(3,4-dimethoxy-phenyl)pyrido[3,2-d]pyrimidine

2-amino-4-{4-[N-(tert-butoxycarbonyl)glycyl]piperazin-1-yl}-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-(N-piperazin-1-yl)-6-(4-fluorophenyl)-pyrido-[3,2-d]pyrimidine

2-amino-4-[4-(2-naphthoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(3-methylphenoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(3-chlorophenoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(2,4-dichlorophenoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(4-fluorophenoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(4-bromophenoxy-acetyl)piperazin-1-yl]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-acetylamino-4-(N-piperazin-1-yl)-6-chloro-pyrido[3,2-d]pyrimidine 2-amino-4-(N-piperazin-1-yl)-6-chloro-pyrido[3,2-d]pyrimidine

2-amino-4-[4-(4-chlorophenoxy-acetyl)piperazin-1-yl]-6-chloro-pyrido[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(4-cyanophenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(4-trifluoromethylphenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(3-fluorophenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(furan-3-yl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(thiophen-3-yl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(3,4-difluorophenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(4-chlorophenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(3-chlorophenyl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(pyridin-4-yl)pyrido-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(3-chloro-4-fluorophenyl)pyri-do-[3,2-d]pyrimidine

2-amino-4-[N-(4-chlorophenoxyacetyl)piperazin-1-yl]-6-(propen-1-yl)pyrido-[3,2-d]pyrimidine

2-amino-6-(4-fluorophenyl)-pyrido(3,2-d)pyrimidin-4(3H)thione

2-amino-4-thiomethyl-6-(4-fluorophenyl)-pyrido(3,2-d)pyrimidine

2-amino-4-thioethyl-6-(4-fluorophenyl)pyrido(3,2-d)pyrimidine

2-amino-4-thioisopropyl-6-(4-fluorophenyl)pyrido(3,2-d)pyrimidine

2-amino-4-(2-methoxy-thioethyl)-6-(4-fluorophenyl)pyrido(3,2-d)pyrimidine

2-acetamido-4-ethylamino-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-isopropylamino-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-(2-methoxy-ethylamino)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-[3,4-(methylenedioxy)anilino]-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-(thiomorpholino-1,1-dioxide)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-(tetrahydro-3-thiophen-amino-1,1-dioxide)-6-(4-fluorophenyl)pyri-do[3,2-d]pyrimidine

2-amino-4-ethylamino-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-isopropylamino-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(2-methoxyethylamino)-6-(4-fluorophenyl)pyrido[3,2-d]

2-amino-4-[3,4-(methylenedioxy)anilino]-6-(4-fluorophenyl)pyrido[3,2-d]

2-amino-4-(thiomorpholino-1,1-dioxide)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(tetrahydro-3-thiophen-amine-1,1-dioxide)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-[1-(4-acetyl-piperazin-1-yl)-3-amino-propan-1-one)]-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-[2-amino-1-(4-methylpiperazin-1-yl)ethanone]-6-(4-fluorophenyl)pyri-do[3,2-d]pyrimidine

2-acetamido-4-(3-methanesulfonyl-propylamino)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-acetamido-4-(2-amino-ethylmethylsulfone)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[1-(4-acetyl-piperazin-1-yl)-3-amino-propan-1-one]-6-(4-fluorophenyl)pyri-do[3,2-d]pyrimidine

2-amino-4-[2-amino-1-(4-methylpiperazin-1-yl)ethanone]-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[(3-methanesulfonyl)-propylamino]-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[(2-amino-ethyl)methylsulfone]-6-(4-fluorophenyl)pyrido[3,2-d]

2-amino-4-(2-butoxy-ethoxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(2-fluoro-ethoxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-[2-(methoxyethoxy)ethoxy]-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(2-chloro-benzyloxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(4-fluoro-benzyloxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(3-methyl-benzyloxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(4-trifluoromethyl-benzyloxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-amino-4-(4-cyano-benzyloxy)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H)one

4-chloro-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-amino-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine)

4-morpholino-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-phenoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-ethoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-[3,4-(methylenedioxy)anilino]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-[2-(N,N-dimethylamino)ethoxy]-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

4-(2-methoxyethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

3-amino-6-(4-fluorophenyl)-pyridine-2-carboxylic acid amide

2-methyl-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H) one

2-ethyl-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H) one

2-chloromethyl-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H)one

2-methyl-4-chloro-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-methyl-4-(N,N-diethylamino)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

3-amino-6-(3-fluorophenyl)-pyridine-2-carboxylic acid amide

2,4-dihydroxy-6-(3-fluorophenyl)-pyrido[3,2-d]pyrimidine

2,4-dihydroxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2,4-dichloro-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-methyl-4-amino-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2,4-diethoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2,4-diisopropoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimi-dine

2,4-di-(2-methoxy-ethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-methyl-4-(2-methoxyethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-chloro-4-(3-methoxypropylamino)-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

2-chloro-4-ethylamino-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-ethyl-4-(2-methoxyethoxy)-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-chloro-4-isopropoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine

2-methyl-4-ethoxy-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimi-dine

N-(4,6-dichloro-pyrido[3,2-d]pyrimidin-2-yl)-acetamide

6-chloro-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-phenyl-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-pyridin-4-yl-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-p-tolyl-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-(4-trifluoromethyl-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-(3-fluoro-4-methoxy-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,4-difluoro-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-(4-methoxy-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-chloro-4-fluoro-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-chloro-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-chloro-3-fluoro-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-amino-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-amino-4-ethoxy-pyrido[3,2-d]pyrimidin-6-yl)-benzonitrile

4-Ethoxy-6-thiophen-2-yl-pyrido[3,2-d]pyrimidin-2-ylamine

6-chloro-4-[1,2,4]triazol-1-yl-pyrido[3,2-d]pyrimidin-2-ylamine

6-chloro-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4,6-bis-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,4-dimethoxy-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-phenyl-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-pyridin-4-yl-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-p-tolyl-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-(4-trifluoromethyl-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-fluoro-4-methoxy-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,4-difluoro-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4-ethoxy-6-(4-methoxy-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-chloro-4-fluoro-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-chloro-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-amino-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-thiophen-2-yl-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-chloro-3-fluoro-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenol

2-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenol

6-(2,4-difluoro-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

N-{4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenyl}-2,2-dimethyl-propionamide

6-(4-methanesulfonyl-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

N-{4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenyl}-isobutyramide

6-(2,4-dimethyl-thiazol-5-yl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(5,6-dihydro-4H-[1,3]oxazin-2-yl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-isopropoxy-phenyl)-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-2-ylamine

4-(2-methoxy-ethoxy)-6-(morpholine-4-sulfonyl)-pyrido[3,2-d]pyrimidin-2-ylamine

{4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenyl}-methanol

{4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenyl}-acetonitrile

N-{4-[2-amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-phenyl}-methanesulfonamide

N-{4-[2-Amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-benzyl}-acetamide

N-{4-[2-Amino-4-(2-methoxy-ethoxy)-pyrido[3,2-d]pyrimidin-6-yl]-benzyl}-methanesulfonamide

6-chloro-4-morpholin-4-yl-pyrido[3,2-d]pyrimidin-2-ylamine

N-[4-(2-amino-4-morpholin-4-yl-pyrido[3,2-d]pyrimidin-6-yl)-phenyl]-acetanide

N-[4-(2-amino-4-morpholin-4-yl-pyrido[3,2-d]pyrimidin-6-yl)-phenyl]-isobutyramide

6-(4-amino-phenyl)-4-morpholin-4-yl-pyrido[3,2-d]pyrimidin-2-ylamine

N-[4-chloro-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidin-2-yl]-acetamide

6-(4-fluoro-phenyl)-4-methoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-fluoro-phenyl)-4-(N-2-methoxyethyl-N-methyl)-pyrido[3,2-d]pyrimidine-2,4-diamine

N-[2-amino-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidin-4-yl]-O-ethyl-hydroxylamine

6-(2-methoxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-[4-(N-methylamido)-phenyl]-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-[4-(N-cyclopropylamido)-phenyl]-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,4-bis(trifluoromethyl)phenyl]-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-methylsulphonylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-chlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(furan-2-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(thiophen-3-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-(morpholinomethyl)phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,3-dichlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-(trifluoromethyl)phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-ethoxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,5-difluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-cyanophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,5-difluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-chlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,5-di(trifluoromethyl)phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(pyrazol-4-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-fluoro-pyridin-3-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,3,4-trifluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-benzyloxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,4,6-trimethylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-fluoro,4-methoxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-methyl,4-fluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-hydroxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-dimethylaminophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-chloro-4-trifluoromethyl-phenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-chloro-3-trifluoromethylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(quinolin-3-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(4-benzyloxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-chloro-5-trifluoromethylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-cyanothiophen-5-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,3-difluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-methylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-trifluoromethylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,4-dichlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,5-dimethylphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,4,5-trifluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(5-chlorothiophen-2-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-methoxypyridin-5-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,4-dichlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3,5-dichlorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(3-ethoxyphenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2,4-difluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-chloro-4-fluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(1-benzothiophen-2-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(furan-3-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(2-methoxy-5-fluorophenyl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(pyrazol-3-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin-2-ylamine

6-(1-benzofuran-2-yl)-4-ethoxy-pyrido[3,2-d]pyrimidin