Macrocyclic indole derivatives useful as hepatitis C virus inhibitors

• US 9,427,440 B2
• Filed: 03/15/2013
• Issued: 08/30/2016
• Est. Priority Date: 07/08/2008
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Inventors: Vendeville, Sandrine Marie Helene, Raboisson, Pierre Jean-Marie Bernard, Lin, Tse-I, Tahri, Abdellah, Amssoms, Katie Ingrid Eduard
• Primary Examiner(s): JARRELL, NOBLE E
• Application Number:
  US13/836,168
• Publication Number:
  US 20140107101A1
• Time in Patent Office: 1,264 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 513/14 Ortho-condensed systems
• CPC Class Codes: C07D 513/18 Bridged systems
• CPC Class Codes: C07D 513/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 515/18 Bridged systems

Abstract

Inhibitors of HCV replication of formula (I)

including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R¹, R², R⁴, R⁵, R⁶ and R⁷ have the meaning defined in the claims.

The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

Claims

1. A method for inhibiting HCV replication, comprising administering to a subject in need thereof a compound of Formula (I)

2. The method of claim 1, wherein the,

R¹ is selected from —

N(R³)—

(CH₂)₄—

N(R³)—

,

3. The method of claim 1, wherein R² is positioned the benzene group in para with respect to the bond linking this benzene to the indole group.

4. The method of claim 1 wherein R² is selected from fluoro and methoxy.

5. The method of claim 1 wherein R⁷ is selected from cyclohexyl and 2-fluorocyclohexyl.

6. The method of claim 1 wherein R⁴ and R⁵ together form a double bond.

7. The method of claim 1 wherein the compounds of formula (I) have the stereochemical configuration as illustrated by formula (IA)

8. The method of claim 1, wherein said compound has one of the structural formula II-1, II-2, II-3, III-1, III-2, III-3, III-4, IV-1, IV-2 or IV-3

9. The method of claim 1, wherein macrocycle A has 17 or 18 member atoms.

10. The method of claim 1, wherein the compound is

11. The method of claim 10, wherein the compound is

12. The method of claim 1, comprising administering to said subject at least one other anti-HCV compound.

13. The method of claim 10, comprising administering to said subject at least one other anti-HCV compound.