Compounds, compositions and methods for treatment of hepatitis C

• US 5,633,388 A
• Filed: 03/29/1996
• Issued: 05/27/1997
• Est. Priority Date: 03/29/1996
• Status: Expired due to Fees

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: ViroPharma Inc. (Shire plc)
• Inventors: Bailey, Thomas R., Diana, Guy D.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Rao, Deepak R.
• Application Number:
  US08/625,717
• Time in Patent Office: 424 Days
• Field of Search: 514/393, 514/394, 514/415, 548/302.7, 548/305.4, 548/305.7, 548/455, 548/309.7
• US Class Current: 548/305.7
• CPC Class Codes: C07D 235/18 with aryl radicals directly attached in position 2
• CPC Class Codes: C07D 235/20 Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical

Abstract

Heterocyclic substituted carboxamides are useful in prophylaxis and treatment of hepatitis C virus infections.

Claims

1. A compound having the formula:

##STR16## wherein Q is an arylene moiety of the formula;

##STR17## wherein R₁, R₂, R₃ and R₄ are the same or different and represent substituents selected from the group consisting of hydrogen, alkyl (C₁ -C₆), halogen, hydroxy, alkoxy, carboxy, carbalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino, acetamido, sulfonamido, alkylamino, dialkylamino and NO₂ ;

R and R'"'"' are the same or different and represent hydrogen or an alkyl (C₁ -C₆) group;

Y and Y'"'"' represent the same or different divalent moieties selected from the group consisting of alkylene (C₃ -C₅) and phenylene, said Y and Y'"'"' moieties being unsubstituted or substituted with at least one alkyl group (C₁ -C₆);

Z and Z'"'"' represent the same or different substituent having the formula;

##STR18## wherein R₅ represents a substituent selected from the group consisting of hydrogen, alkyl (C₁ -C₆) and acyl, and each R₆ is the same or different and represents a substituent selected from the group consisting of hydrogen, alkyl (C₁ -C₆), halogen, hydroxy, alkoxy, carboxy, carbalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino, acetamido, sulfonamido, alkylamino, dialkylamino and NO₂, with m being 1-4, and the isomers and pharmaceutically acceptable salts of said compound.

2. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,4-benzenedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 1.

10. A pharmaceutical composition for treating hepatitis C virus infection, said composition comprising a compound as claimed in claims 1 and 3 in an amount effective to attenuate infectivity of said virus, and a pharmaceutically acceptable carrier medium.

11. A composition as claimed in claim 10 in the form of a solid with a pharmaceutically acceptable excipient.

12. A composition as claimed in claim 10 in the form of a liquid with a pharmaceutically acceptable diluent.

13. A composition as claimed in claim 10 comprising from about 1 to about 50 mg of said compound by weight of said composition.

14. A method of treatment of hepatitis C virus infection in a patient in need of said treatment, said method comprising administering to said patient a therapeutically effective amount of a compound as claimed in claims 1 or 3.

15. A method as claimed in claim 14, wherein said compound is administered in unit dosage form containing about 1 to about 10 mg of said compound per kilogram of patient body weight per day.

16. A method as claimed in claim 15, wherein said unit dosage includes a pharmaceutically acceptable carrier medium.

17. A method as claimed in claim 14, wherein said compound is administered parenterally.

18. A method as claimed in claim 14, wherein said compound is administered orally.

19. A method of preventing hepatitis C virus infection in a host susceptible to said infection, said method comprising administering to said host a prophylactically effective amount of a compound as claimed in claims 1 or 3.

20. A method as claimed in claim 19, wherein said compound is administered in unit dosage form containing about 1 to about 10 mg of said compound per kilogram of patient body weight per day.

21. A method as claimed in claim 20, wherein said unit dosage includes a pharmaceutically acceptable carrier medium.

22. A method as claimed in claim 19, wherein said composition is administered parenterally.

23. A method as claimed in claim 19, wherein said composition is administered orally.

3. A compound having the formula:

##STR19## wherein Q is a divalent moiety selected from the group consisting of straight or branched, unsubstituted or substituted C₁ -C₁₂ alkylene, straight or branched, unsubstituted or substituted C₂ -C₁₂ alkenylene, straight or branched, unsubstituted or substituted C₁ -C₁₂ alkylene interrupted with oxygen, nitrogen or sulfur, straight or branched, unsubstituted or substituted C₂ -C₁₂ alkenylene interrupted with oxygen, nitrogen or sulfur, said alkylene and alkenylene moiety substituents being selected from at least one of the group consisting of alkyl (C₁ -C₆), amino, alkylamino, dialkylamino or acetamido;

R and R'"'"' are the same or different and represent hydrogen or an alkyl (C₁ -C₆) group;

Y and Y'"'"' represent the same or different divalent moieties selected from the group consisting of alkylene (C₃ -C₅) and phenylene, said Y and Y'"'"' moieties being unsubstituted or substituted with at least one alkyl group (C₁ -C₆);

Z and Z'"'"' represent the same or different substituent having the formula;

##STR20## wherein R₅ represents a substituent selected from the group consisting of hydrogen, alkyl (C₁ -C₆) and acyl, and each R₆ is the same or different and represents a substituent selected from the group consisting of hydrogen, alkyl (C₁ -C₆), halogen, hydroxy, alkoxy, carboxy, carbalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino, acetamido, sulfonamido, alkylamino, dialkylamino and NO₂, with m being 1-4, and the isomers and pharmaceutically acceptable salts of said compound.

4. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,4-butanedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.

5. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,6-hexanedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.

6. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,8-octanedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.

7. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,9-nonanedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.

8. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,10-decanedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.

9. The compound N,N'"'"'-4-[(2-benzimidazole)phenyl]-1,4-butenedicarboxamide and the pharmaceutically acceptable salts of said compound, as claimed in claim 3.