4,6-di- and 2,4,6-trisubstituted quinazoline derivatives and pharmaceutical compositions useful for treating viral infections

• US 8,673,929 B2
• Filed: 07/20/2007
• Issued: 03/18/2014
• Est. Priority Date: 07/20/2006
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Gao, Ling-Jie, De Jonghe, Steven Cesar Alfons, Watkins, William John, Chong, Lee Shun, Herdewijn, Piet Andr Maurits Maria
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US12/374,242
• Publication Number:
  US 20100143299A1
• Time in Patent Office: 2,433 Days
• Field of Search: 544/283, 544/284, 544/285, 544/286, 544/287, 514/266.1
• US Class Current: 514/266.1
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07D 239/90 with acyclic radicals attached in position 2 or 3
• CPC Class Codes: C07D 239/95 with hetero atoms directly attached in positions 2 and 4
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond

Abstract

This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R₂ is selected from the group consisting of hydrogen, NR′R″ and C_1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O)_n, C_1-7 alkylene, C_2-7 alkenylene and C_2-7 alkynylene; R₄ is selected from the group consisting of C_1-7 alkyl, C_2-7 alkenyl, C_3-10cycloalkyl, C_3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C_1-7 alkylene, C_2-7 alkenylene, and C_2-7 alkynylene; n is 0, 1 or 2; and R₆ is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

Claims

1. A 4,6-disubstituted or 2,4,6-trisubstituted quinazoline represented by the structural formula (I)

3. A quinazoline according to claim 1, wherein R₂ is NR′

R″

, and R′ and

R″

are each hydrogen.

4. A quinazoline according to claim 1, wherein R₂ is NR′

R″

, and R′

is hydrogen and R″

is phenyl optionally substituted with one or more halogens.

5. A quinazoline according to claim 1, wherein R₄ is C_1-4 alkyl optionally substituted with one or more R₇.

6. A quinazoline according to claim 1, wherein R₆ is heteroaryl or phenyl optionally substituted with one or more R₈.

7. A quinazoline according to claim 5, wherein R₄ is C_1-4 alkyl substituted with one or more R₇, and R₇ is selected from the group consisting of halogen, cyano, C_1-7 alkyl optionally substituted with one or more halogen, C_1-7 alkoxy optionally substituted with one or more halogen, —

CO—

NHR₉, —

NR₁₂—

COR₁₀, cycloalkyl, aryl, aryloxy and heterocyclyl.

8. A quinazoline according to claim 6, wherein R₆ is heteroaryl or phenyl substituted with one or more R₈, and R₈ is selected from the group consisting of halogen, cyano, C_1-7 alkyl optionally substituted with one or more halogen, C_1-7 alkoxy optionally substituted with one or more halogen, —

CO—

NHR₉, —

NR₁₂—

COR₁₀, cycloalkyl, aryl, aryloxy and heterocyclyl.

9. A quinazoline according to claim 8, wherein R₉ is selected from the group consisting of hydrogen;

C_3-10cycloalkyl optionally substituted with cyano;

C_1-7alkyl optionally substituted with one or more substituents selected from the group consisting of dialkylamino, halogen and heterocyclyl optionally substituted with C_1-7alkyl;

heterocyclyl;

aryl and arylC_1-7 alkyl wherein the aryl moiety is optionally substituted with one or more halogens.

10. A quinazoline according to claim 8, wherein R₁₀ is C_1-7 alkyl and R₁₂ is hydrogen.

12. A pharmaceutical composition comprising a quinazoline according to claim 1, and one or more pharmaceutically acceptable excipients.

14. A pharmaceutical composition according to claim 12, further comprising one or more other antiviral agents.

15. A pharmaceutical composition according to claim 12, further comprising one or more antiviral agents selected from the group consisting of interferon alpha, ribavirin, NS3 protease inhibitors, and nucleoside- or non-nucleoside-based inhibitors of NS5B polymerase.

16. A method of treating a Flaviviridae viral infection by administering to a patient in need thereof a therapeutically effective amount of a quinazoline according to claim 1.

18. A process for preparing a quinazoline according to claim 1, comprising the step of reacting (a) a quinazoline intermediate having a group R₂ in position 2 of the quinazoline scaffold, a chloro or 1,2,4-triazolyl group in position 4 of the quinazoline scaffold, and a group Y—

R₆ or halogen in position 6 of the quinazoline scaffold with (b) a nucleophilic reagent R₄AM, wherein M is an alkaline metal, under conditions suitable to produce the quinazoline.

2. A quinazoline selected from the group consisting of:

2-amino-6-(3,4-dimethoxyphenyl)-4-hydroxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-(2-methoxyethoxy)-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-isopropoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-(trifluoromethoxy)-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-ethoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-methoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-butoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-sec-butoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-tert-butoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-propoxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-benzyloxy-quinazoline,

2-amino-6-(3,4-dimethoxyphenyl)-4-cyclopentyloxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-hydroxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-(2-methoxyethoxy)-quinazoline,

2-amino-6-(4-fluorophenyl)-4-isopropoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-amino-6-(4-fluorophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-amino-6-(4-fluorophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-amino-6-(4-fluorophenyl)-4-(trifluoromethoxy)-quinazoline,

2-amino-6-(4-fluorophenyl)-4-ethoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-methoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-butoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-sec-butoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-tert-butoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-propoxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-benzyloxy-quinazoline,

2-amino-6-(4-fluorophenyl)-4-cyclopentyloxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-hydroxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-isopropoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-(2-methoxyethoxy)-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-ethoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-(trifluoromethoxy)-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-methoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-butoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-sec-butoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-tert-butoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-propoxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-benzyloxy-quinazoline,

2-amino-6-(4-acetamidophenyl)-4-cyclopentyloxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-hydroxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-(2-methoxyethoxy)-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-isopropoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-(trifluoromethoxy)-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-ethoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-methoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-butoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-sec-butoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-tert-butoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-propoxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-benzyloxy-quinazoline,

2-acetamino-6-(3,4-dimethoxyphenyl)-4-cyclopentyloxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-hydroxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-(2-methoxyethoxy)-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-isopropoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-(trifluoromethoxy)-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-ethoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-methoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-butoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-sec-butoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-tert-butoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-propoxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-benzyloxy-quinazoline,

2-acetamino-6-(4-fluorophenyl)-4-cyclopentyloxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-hydroxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-isopropoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-(2-methoxyethoxy)-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-ethoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-(trifluoromethoxy)-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-methoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-butoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-sec-butoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-tert-butoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-propoxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-benzyloxy-quinazoline,

2-acetamino-6-(4-acetamidophenyl)-4-cyclopentyloxy-quinazoline,

6-(2,3-Difluoro-phenyl)-4-ethoxy-quinazolin-2-ylamine,

4-Ethoxy-6-p-tolyl-quinazolin-2-ylamine,

4-Ethoxy-6-furan-3-yl-quinazolin-2-ylamine,

4-Ethoxy-6-(2H-pyrazol-3-yl)-quinazolin-2-ylamine,

4-Ethoxy-6-thiophen-2-yl-quinazolin-2-ylamine,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-methyl-benzamide,

4-Ethoxy-6-furan-2-yl-quinazolin-2-ylamine,

4-Ethoxy-6-thiophen-3-yl-quinazolin-2-ylamine,

6-(3,4-Difluoro-phenyl)-4-ethoxy-quinazolin-2-ylamine,

3-(2-Amino-4-ethoxy-quinazolin-6-yl)-benzonitrile,

4-Ethoxy-6-(2H-pyrazol-4-yl)-quinazolin-2-ylamine,

6-(4-Amino-phenyl)-4-ethoxy-quinazolin-2-ylamine,

4-Ethoxy-6-(2,3,4-trifluoro-phenyl)-quinazolin-2-ylamine,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenol,

6-(2,3-Difluoro-phenyl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-(2-Methoxy-ethoxy)-6-(2-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

6-(5-Chloro-thiophen-2-yl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-(2-Methoxy-ethoxy)-6-p-tolyl-quinazolin-2-ylamine,

6-Benzo[b]thiophen-2-yl-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

6-Benzofuran-2-yl-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-(2-Methoxy-ethoxy)-6-thiophen-2-yl-quinazolin-2-ylamine,

4-(2-Amino-4-(2-methoxy-ethoxy)-quinazolin-6-yl)-N-methyl-benzamide,

4-(2-Methoxy-ethoxy)-6-furan-2-yl-quinazolin-2-ylamine,

4-(2-Methoxy-ethoxy)-6-thiophen-3-yl-quinazolin-2-ylamine,

6-(3,4-Difluoro-phenyl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

3-(2-Amino-4-(2-methoxy-ethoxy)-quinazolin-6-yl)-benzonithle,

4-(2-Methoxy-ethoxy)-6-(2H-pyrazol-4-yl)-quinazolin-2-ylamine,

6-(4-Amino-phenyl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-(2-Methoxy-ethoxy)-6-(2,3,4-trifluoro-phenyl)-quinazolin-2-ylamine,

6-(4-Fluoro-2-methyl-phenyl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-[2-Amino-4-(2-methoxy-ethoxy)-quinazolin-6-yl]-phenol,

6-(4-Chloro-3-trifluoromethyl-phenyl)-4-(2-methoxy-ethoxy)-quinazolin-2-ylamine,

4-Benzyloxy-6-(2H-pyrazol-3-yl)-quinazolin-2-ylamine,

4-(2-Amino-4-benzyloxy-quinazolin-6-yl)-N-methyl-benzamide,

4-Benzyloxy-6-(1H-pyrazol-4-yl)-quinazolin-2-ylamine,

4-[2-(2-Dimethylamino-ethoxy)-ethoxy]-6-(4-trifluoromethoxy-phenyl)-quinazolin-2-ylamine,

6-(2,4-Difluoro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

6-(2,3-Difluoro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-(3-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

4-Isopropoxy-6-(2-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

4-Isopropoxy-6-(4-chloro-phenyl)-quinazolin-2-ylamine,

4-Isopropoxy-6-p-tolyl-quinazolin-2-ylamine,

6-(2,4-Dichloro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

6-(2-Chloro-4-fluoro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

6-(3-Chloro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

6-Benzo[b]thiophen-2-yl-4-isopropoxy-quinazolin-2-ylamine,

6-Furan-3-yl-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-(2H-pyrazol-3-yl)-quinazolin-2-ylamine,

6-Benzofuran-2-yl-4-isopropoxy-quinazolin-2-ylamine,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-methyl-benzamide,

6-Furan-2-yl-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-thiophen-3-yl-quinazolin-2-ylamine,

4-Isopropoxy-6-pyridin-3-yl-quinazolin-2-ylamine,

6-(3,4-Difluoro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-pyridin-4-yl-quinazolin-2-ylamine,

3-(2-Amino-4-isopropoxy-quinazolin-6-yl)-benzonitrile,

6-(3,5-Difluoro-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-(4-trifluoromethoxy-phenyl)-quinazolin-2-ylamine,

6-(4-Amino-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

4-Isopropoxy-6-(2,3,4-trifluoro-phenyl)-quinazolin-2-ylamine,

6-(2-Benzyloxy-phenyl)-4-isopropoxy-quinazolin-2-ylamine,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-benzonitrile,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-phenol,

4-Isopropoxy-6-quinolin-3-yl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2,4-difluoro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(4-fluoro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2,3-difluoro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-o-tolyl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(3-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-p-tolyl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2,4-dichloro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(4-ethoxy-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2-chloro-4-fluoro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-furan-3-yl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(3-chloro-4-fluoro-phenyl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2H-pyrazol-3-yl)-quinazolin-2-ylamine,

6-Benzofuran-2-yl-4-cyclobutylmethoxy-quinazolin-2-ylamine,

4-(2-Amino-4-cyclobutylmethoxy-quinazolin-6-yl)-N-methyl-benzamide,

4-Cyclobutylmethoxy-6-furan-2-yl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-thiophen-3-yl-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-pyridin-3-yl-quinazolin-2-ylamine,

3-(2-Amino-4-cyclobutylmethoxy-quinazolin-6-yl)-benzonitrile,

4-Cyclobutylmethoxy-6-(2H-pyrazol-4-yl)-quinazolin-2-ylamine,

4-Cyclobutylmethoxy-6-(2,3,4-trifluoro-phenyl)-quinazolin-2-ylamine,

4-(2-Amino-4-cyclobutylmethoxy-quinazolin-6-yl)-benzonitrile,

4-(2-Amino-4-cyclobutylmethoxy-quinazolin-6-yl)-phenol,

6-(2-Chloro-4-trifluoromethyl-phenyl)-4-cyclobutylmethoxy-quinazolin-2-ylamine,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N,N-dimethyl-benzamide,

[4-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenyl]-pyrrolidin-1-yl-methanone,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N,N-dimethyl-benzamide,

[4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-phenyl]-morpholin-4-yl-methanone,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-benzyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-isobutyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-cyclohexyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-butyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-tert-butyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-cyclopentyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-isopropyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-methoxy-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-furan-2-ylmethyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-(2-dimethylamino-ethyl)-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-pyridin-2-yl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-(4-fluoro-phenyl)-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-(4,5-dihydro-thiazol-2-yl)-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-2-chloro-N-methyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-2-chloro-N-cyclopropyl-benzamide,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-phenol,

3-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-phenol,

4-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-cyclopropyl-benzamide,

3-(2-Amino-4-cyclopropylmethoxy-quinazolin-6-yl)-N-methyl-benzamide,

[4-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenyl]-piperidin-1-yl-methanone,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-benzyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-isobutyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-cyclohexyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-butyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-tert-butyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-cyclopentyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-isopropyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-methoxy-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-furan-2-ylmethyl-benzamide,

[4-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenyl]-thiazolidin-3-yl-methanone,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-(2-dimethylamino-ethyl)-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-pyridin-2-yl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-(4-fluoro-phenyl)-benzamide,

[4-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenyl]-thiomorpholin-4-yl-methanone,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-(4,5-dihydro-thiazol-2-yl)-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-2-chloro-N-methyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-2-chloro-N-cyclopropyl-benzamide,

3-(2-Amino-4-ethoxy-quinazolin-6-yl)-phenol,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-cyclopropyl-benzamide,

3-(2-Amino-4-ethoxy-quinazolin-6-yl)-N-methyl-benzamide,

[4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-phenyl]-piperidin-1-yl-methanone,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-benzyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-isobutyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-cyclohexyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-butyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-tert-butyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-cyclopentyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-isopropyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-methoxy-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-(2-dimethylamino-ethyl)-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-(4-fluoro-phenyl)-benzamide,

[4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-phenyl]-thiomorpholin-4-yl-methanone,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-(4,5-dihydro-thiazol-2-yl)-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-2-chloro-N-methyl-benzamide,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-2-chloro-N-cyclopropyl-benzamide,

3-(2-Amino-4-isopropoxy-quinazolin-6-yl)-phenol,

4-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-cyclopropyl-benzamide,

3-(2-Amino-4-isopropoxy-quinazolin-6-yl)-N-methyl-benzamide,

4-Ethoxy-6-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-quinazolin-2-ylamine,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-N-isobutyl-benzamide,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-N-cyclopentyl-benzamide,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-N-isopropyl-benzamide,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-N-methoxy-benzamide,

{4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-phenyl}-thiazolidin-3-yl-methanone,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-phenol,

3-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-phenol,

4-[2-Amino-4-(2-hydroxy-ethoxy)-quinazolin-6-yl]-N-cyclopropyl-benzamide,

{4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-phenyl}-piperidin-1-yl-methanone,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-benzyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-isobutyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-butyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-tert-butyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-cyclopentyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-isopropyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-methoxy-benzamide,

{4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-phenyl}-thiazolidin-3-yl-methanone,

{4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-phenyl}-thiomorpholin-4-yl-methanone,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-(4,5-dihydro-thiazol-2-yl)-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-2-chloro-N-methyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-2-chloro-N-cyclopropyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-phenol,

3-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-phenol,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-cyclopropyl-benzamide,

4-[2-Amino-4-(2-fluoro-ethoxy)-quinazolin-6-yl]-N-methyl-benzamide,

(S)-4-[2-Amino-4-(tetrahydro-furan-2-ylmethoxy)-quinazolin-6-yl]-N-cyclopropyl-benzamide,

4-(2-Amino-4-ethoxy-quinazolin-6-yl)-benzamide,

(S)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-cyclopropyl-benzamide,

(S)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(2-dimethylamino-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(2-morpholin-4-yl-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(2-pyrrolidin-1-yl-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(2,2,2-trifluoro-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(3-pyrrolidin-1-yl-propyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(1,1-dimethyl-2-pyrrolidin-1-yl-ethyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(1-cyano-cyclopropyl)-benzamide,

(R)-4-[2-Amino-4-(tetrahydro-furan-3-yloxy)-quinazolin-6-yl]-N-(1-isopropyl-piperidin-4-yl)-benzamide,

6-(2,4-Bis-trifluoromethyl-phenyl)-4-(3-dimethylamino-propoxy)-quinazolin-2-ylamine,

6-Benzofuran-2-yl-4-(3-dimethylamino-propoxy)-quinazolin-2-ylamine,

6-(3-Chloro-4-fluoro-phenyl)-4-(3-dimethylamino-propoxy)-quinazolin-2-ylamine,

6-(2,4-Dichloro-phenyl)-4-(3-dimethylamino-propoxy)-quinazolin-2-ylamine,

4-(3-Dimethylamino-propoxy)-6-(3,4,5-trifluoro-phenyl)-quinazolin-2-ylamine,

4-(3-Dimethylamino-propoxy)-6-(3,5-dimethyl-phenyl)-quinazolin-2-ylamine,

6-(4-Chloro-phenyl)-4-(3-dimethylamino-propoxy)-quinazolin-2-ylamine,

4-(3-Dimethylamino-propoxy)-6-(3-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

6-(4-Chloro-3-trifluoromethyl-phenyl)-4-(2-morpholin-4-yl-ethoxy)-quinazolin-2-ylamine,

4-[2-Amino-4-(2-morpholin-4-yl-ethoxy)-quinazolin-6-yl]-phenol,

4-(2-Morpholin-4-yl-ethoxy)-6-thiophen-3-yl-quinazolin-2-ylamine,

4-(2-Morpholin-4-yl-ethoxy)-6-thiophen-2-yl-quinazolin-2-ylamine,

6-Benzofuran-2-yl-4-(2-morpholin-4-yl-ethoxy)-quinazolin-2-ylamine,

6-Furan-3-yl-4-(2-morpholin-4-yl-ethoxy)-quinazolin-2-ylamine,

6-Benzo[b]thiophen-2-yl-4-(2-morpholin-4-yl-ethoxy)-quinazolin-2-ylamine,

4-(2-Morpholin-4-yl-ethoxy)-6-(2-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

4-(2-Morpholin-4-yl-ethoxy)-6-(3-trifluoromethyl-phenyl)-quinazolin-2-ylamine,

6-(2,3-Difluoro-phenyl)-4-(2-morpholin-4-yl-ethoxy)-quinazolin-2-ylamine,

4-{([4-Ethoxy-6-(4-fluoro-phenyl)-quinazolin-2-ylamino]-methyl}-benzenesulfonamide,

4-{([6-(3-Cyclopropanesulfonylamino-4-fluoro-phenyl)-4-ethoxy-quinazolin-2-ylamino]-methyl}-benzenesulfonamide,

4-{([6-(3-aminosulfonyl-phenyl)-4-ethoxy-quinazolin-2-ylamino]-methyl}-benzenesulfonamide,

4-{([4-Ethoxy-6-(4-ureido-phenyl)-quinazolin-2-ylamino]-methyl}-benzenesulfonamide,

N-Cyclopropyl-4-[4-ethoxy-2-(4-sulfamoyl-benzylamino)-quinazolin-6-yl]-benzamide,

or a pharmaceutically acceptable addition salt thereof or a stereoisomer thereof or a mono- or a di-N-oxide thereof.

11. A quinazoline selected from the group consisting of:

6-(3,4-dimethoxyphenyl)-4-hydroxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-(2-methoxyethoxy)-quinazoline,

6-(3,4-dimethoxyphenyl)-4-isopropoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-(cyclopropyl-methoxy)-quinazoline,

6-(3,4-dimethoxyphenyl)-4-(2-(4-morpholinyl)ethoxy-]-quinazoline,

6-(3,4-dimethoxyphenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

6-(3,4-dimethoxyphenyl)-4-(trifluoromethoxy)-quinazoline,

6-(3,4-dimethoxyphenyl)-4-ethoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-methoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-butoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-sec-butoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-tert-butoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-propoxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-benzyloxy-quinazoline,

6-(3,4-dimethoxyphenyl)-4-cyclopentyloxy-quinazoline,

6-(4-fluorophenyl)-4-hydroxy-quinazoline,

6-(4-fluorophenyl)-4-(2-methoxyethoxy)-quinazoline,

6-(4-fluorophenyl)-4-isopropoxy-quinazoline,

6-(4-fluorophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

6-(4-fluorophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

6-(4-fluorophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

6-(4-fluorophenyl)-4-(trifluoromethoxy)-quinazoline,

6-(4-fluorophenyl)-4-ethoxy-quinazoline,

6-(4-fluorophenyl)-4-methoxy-quinazoline,

6-(4-fluorophenyl)-4-butoxy-quinazoline,

6-(4-fluorophenyl)-4-sec-butoxy-quinazoline,

6-(4-fluorophenyl)-4-tert-butoxy-quinazoline,

6-(4-fluorophenyl)-4-propoxy-quinazoline,

6-(4-fluorophenyl)-4-benzyloxy-quinazoline,

6-(4-fluorophenyl)-4-cyclopentyloxy-quinazoline,

6-(4-acetamidophenyl)-4-hydroxy-quinazoline,

6-(4-acetamidophenyl)-4-isopropoxy-quinazoline,

6-(4-acetamidophenyl)-4-(2-methoxyethoxy)-quinazoline,

6-(4-acetamidophenyl)-4-[2-(4-morpholinyl)ethoxy]-quinazoline,

6-(4-acetamidophenyl)-4-ethoxy-quinazoline,

6-(4-acetamidophenyl)-4-(cyclopropyl-methoxy)-quinazoline,

6-(4-acetamidophenyl)-4-(2,2,2-trifluoroethoxy)-quinazoline,

6-(4-acetamidophenyl)-4-(trifluoromethoxy)-quinazoline,

6-(4-acetamidophenyl)-4-methoxy-quinazoline,

6-(4-acetamidophenyl)-4-butoxy-quinazoline,

6-(4-acetamidophenyl)-4-sec-butoxy-quinazoline,

6-(4-acetamidophenyl)-4-tert-butoxy-quinazoline,

6-(4-acetamidophenyl)-4-propoxy-quinazoline,

6-(4-acetamidophenyl)-4-benzyloxy-quinazoline,

6-(4-acetamidophenyl)-4-cyclopentyloxy-quinazoline,

4-isopropoxy-6-thiophen-3-yl-quinazoline,

4-(4-Isopropoxy-quinazolin-6-yl)-N-methyl-benzamide,

4-(4-(2-methoxyethoxy)-quinazolin-6-yl)-N-methyl-benzamide,

4-ethoxy-6-(1H-pyrazol-4-yl)-quinazoline,

6-(4-fluorophenyl)-4-isopropoxy-quinazoline,

(S)-4-(2-(4-fluorobenzylamino)-4-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamide,

Pyrrolidine-1-carboxylic acid (4-[4-ethoxy-2-(4-sulfamoyl-benzylamino)-quinazolin-6-yl]-phenyl]-amide,

4-[4-Ethoxy-2-(4-sulfamoyl-benzylamino)-quinazolin-6-yl]-benzamide,

4-Ethoxy-2-(4-fluorobenzylamino)-6-(4-fluoro-phenyl)-quinazoline,

N-Cyclopropyl-4-[4-ethoxy-2-(4-fluorobenzylamino)-quinazolin-6-yl]-benzamide, and

6-(4-fluorophenyl)-4-propyl-quinazoline,

or a pharmaceutically acceptable addition salt thereof or a stereoisomer thereof or a mono- or a di-N-oxide thereof.

13. A pharmaceutical composition comprising 4-ethoxy-6-(4-fluorophenyl)-quinazoline and one or more pharmaceutically acceptable excipients.

17. A method of treating a Flaviviridae viral infection by administering to a patient in need thereof a therapeutically effective amount of 4-ethoxy-6-(4-fluorophenyl)-quinazoline.