Quinazolinone analogs and use of quinazolinone analogs for treating or preventing certain viral infections

Patent metadata

Field	Value
Publication number	US-9598402-B2
Application number	US-201214238346-A
Country	US
Kind code	B2
Filing date	Aug 10, 2012
Priority date	Aug 12, 2011
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

Provided is a process for treating or preventing a viral infection in a subject, wherein the viral infection is from a flavivirus selected from the group consisting of Hepatitis C Virus (genotypes 1-7) and Japanese Encephalitis Virus. The process includes administering to the subject a therapeutically effective amount of at least one compound represented by the formula: (Formula (I))

First claim

What is claimed is:

1. A process for treating or preventing a viral infection in a subject from Hepatitis C Virus, by administering to the subject a therapeutically effective amount of at least one compound selected from the group consisting of 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-(4-phenyl(1,3-thiazol-2-yl))acetamide; N-benzothiazol-5-yl-2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]acetamide; 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-(4-methyl(1,3-thiazol-2-yl))acetamide; N-(2,3-dihydro-1H-inden-5-yl)-2-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide; 2-[3-(3-chloro-4-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-(5-fluoro-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))-N-indan-5-ylacetamide; N-indan-5-yl-2-(8-methyl-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))acetamide; N-indan-5-yl-2-(8-methoxy-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))acetamide; 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-4-ylacetamide; N-(2H-benzo[d]1,3-dioxolen-5-yl)-2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]acetamide; 3-[3-(3-chloro-4-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylpropanamide; 2-[3-(3-chloro-4-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-4-ylacetamide; N-(2H-benzo[3,4-d]1,3-dioxolan-5-yl)-2-[3-(3-chloro-4-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]acetamide; 2-[3-(3,4-difluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-4-ylacetamide; 2-[3-(3,4-difluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-(5-fluoro-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))-N-(1,2,3,4-tetrahydronaphthyl)acetamide; 2-[3-(4-chloro-3-fluorophenyl)-5-fluoro-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[5-fluoro-4-oxo-3-(3,4,5-trifluorophenyl)(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; and 2-[3-(3,4-dichlorophenyl)-5-fluoro-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; pharmaceutically acceptable salts thereof; solvates thereof and deuterated forms thereof.

2. A process for treating or preventing a viral infection in a subject from Japanese Encephalitis Virus by administering to the subject a therapeutically effective amount of at least one compound selected from the group consisting of 2-(5-fluoro-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))-N-indan-5-ylacetamide; 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-4-ylacetamide; 2-[3-(2,6-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; and 2-(8-fluoro-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))-N-indan-5-ylacetamide; pharmaceutically acceptable salts thereof solvates thereof and deuterated forms thereof.

3. A process for treating or preventing a viral infection in a subject from West Nile Virus by administering to the subject a therapeutically effective amount of at least one compound selected from the group consisting of: 2-[3-(2-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3-chloro-4-fluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,5-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,4-difluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide, 2-[3-(3,4-dichlorophenyl)-5-fluoro-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; N-indan-5-yl-2-(4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))acetamide; 2-[3-(4-chloro-3-methylphenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(4-fluoro-3-methylphenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; N-indan-5-yl-2-[4-oxo-3-(3,4,5trifluorophenyl)(3-hydroquinazolin-2-ylthio)]acetamide; 2-[3-(3-bromo-4-methylphenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,4-dichlorophenyl)-8-fluoro-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,5-difluorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3,5-dichlorophenyl)-8-fluoro-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(2,6-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-[3-(3-bromo-4-chlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; 2-(8-fluoro-4-oxo-3-phenyl(3-hydroquinazolin-2-ylthio))-N-indan-5-ylacetamide; and 2-[3-(4,5-difluoro(2-pyridyl))-4-oxo(3-hydroquinazolin-2-ylthio)]-N-indan-5-ylacetamide; pharmaceutically acceptable salts thereof; solvates thereof and deuterated forms thereof.

4. A process for treating or preventing a viral infection in a subject, wherein said viral infection is from a flavivirus selected from the group consisting of Hepatitis C Virus (genotypes 1-7) and Japanese Encephalitis Virus, which comprises administering to said subject a therapeutically effective amount of a compound represented by formula:

wherein W is a substituted or unsubstituted thiazoyl group and when substituted W is substituted with a C 1-6 alkyl, phenyl or benzoyl group, and each R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 is independently selected from the group consisting of H, halogen, hydroxy, amino, nitro, cyano, CF 3 , and C 1-6 alkyl; R 11 and R 12 are independently selected from the group consisting of H, halogen, hydroxyl, C 1-6 alkoxy, amino, nitro, cyano, CF 3 and C 1-4 alkyl; n is zero, one, two, three or four, five or six; pharmaceutically acceptable salts thereof; solvates thereof and deuterated forms thereof.

5. The process for treating or preventing a viral infection in a subject according to claim 4 , wherein each of R 2 , R 3 , R 6 , R 7 , R 8 , R 9 and R 10 is hydrogen and each of R 4 and R 5 is chloro.

6. The process for treating or preventing a viral infection in a subject according to claim 4 , wherein the compound is selected from the group consisting of 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-(4-phenyl(1,3-thiazol-2-yl))acetamide; N-benzothiazol-5-yl-2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]acetamide; and 2-[3-(3,4-dichlorophenyl)-4-oxo(3-hydroquinazolin-2-ylthio)]-N-(4-methyl(1,3-thiazol-2-yl))acetamide; pharmaceutically acceptable salts thereof; solvates thereof and deuterated forms thereof.

7. A process for treating or preventing a viral infection in a subject according to claim 4 , wherein said viral infection is from Hepatitis C Virus.

8. A process for treating or preventing a viral infection in a subject, wherein said viral infection is from a flavivirus selected from the group consisting of Hepatitis C Virus (genotypes 1-7) and Japanese Encephalitis Virus, which comprises administering to said subject a therapeutically effective amount of at least one compound represented by the formula:

wherein R 1 is represented by the formula:

and
each R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 is independently selected from the group consisting of H, halogen, hydroxy, amino, nitro, cyano, formyl, CF 3 , S(C 1-4 alkyl), S(O)C 1-4 alkyl, S(O) 2 C 1-4 alkyl, C 1-4 alkylcarbonyl, C 1-6 alkyl, hydroxy C 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, hydroxy C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylamino, di(C 1-6 alkyl)amino; R 11 and R 12 are independently selected from the group consisting of H, halogen, hydroxyl, C 1-6 alkoxy, amino, nitro, cyano, CF 3

Assignees

• Heil Marintha L
• Cosford Nicholas D P
• Ardecky Robert
• Zou Jiwen
• Southern Res Inst
• Sanford-Burnham Medical Res Inst

Inventors

• Heil Marintha L
• Cosford Nicholas D P
• Ardecky Robert
• Zou Jiwen

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07D239/95 Primary

  with hetero atoms directly attached in positions 2 and 4 · CPC title

• C07D405/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title