Pyrido(3,2-D)pyrimidines and pharmaceutical compositions useful for treating hepatitis C

• US 8,232,278 B2
• Filed: 06/26/2006
• Issued: 07/31/2012
• Est. Priority Date: 06/24/2005
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: De Jonghe, Steven Cesar Alfons, Herdewijn, Piet André Maurits Maria, Lee, William A., Watkins, William John
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US11/993,832
• Publication Number:
  US 20090131414A1
• Time in Patent Office: 2,227 Days
• Field of Search: 544/256, 544/236, 544/258, 514/262.1, 514/247
• US Class Current: 514/262.1
• 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. A compound having the structural formula:

2. A compound according to claim 1, wherein R₁ is not hydrogen.

3. A compound according to claim 1, wherein R₁ is amino or acetamido.

4. A compound according to claim 1, wherein R₁ is amino or acetamido, and further wherein R₃ is a substituted C_6-30 aryl group.

5. A compound according to claim 1, wherein R₁ is amino or acetamido, wherein R₃ is a substituted C_6-30 aryl group and wherein R₄ is hydrogen.

6. A compound according to claim 1, wherein the N-containing C_2-15 heterocyclic of R₂ is selected from the group consisting of N-thiomorpholinyl, N-piperidinyl, N-homopiperidinyl and N-pyrrolidinyl.

8. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a compound according to claim 1 or 7.

9. A pharmaceutical composition according to claim 8, further comprising one or more antiviral agents.

10. A pharmaceutical composition according to claim 9, 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.

11. A pharmaceutical composition according to claim 9, 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, fialuridine, 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.

12. A pharmaceutical composition according to claim 8, 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.

13. A pharmaceutical composition according to claim 8, being for oral, rectal, intramuscular or intraperitoneous administration.

17. A method of treatment 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 compound according to claim 1 or 7.

7. A compound 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-yl])-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]pyrimidine,

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-di-methoxyphenyl)-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)-pyri-do-[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)pyri-midine,

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)pyrido[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]pyrimidine,

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

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)pyrido[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]pyri-midine,

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

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]pyrimi-dine,

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]-acetamide,

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, and

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

or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.

14. A method of treatment 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 compound having the structural formula:

15. The method according to claim 14, wherein said virus belongs to a genus selected from the group consisting of Genus Flavivirus, Genus Hepacivirus and Genus Pestivirus.

16. The method according to claim 14, wherein said infection is hepatitis C.