HCV NS3 protease inhibitors

Patent metadata

Field	Value
Publication number	US-9738661-B2
Application number	US-201514638733-A
Country	US
Kind code	B2
Filing date	Apr 3, 2015
Priority date	Oct 27, 2006
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

First claim

What is claimed is:

1. A compound of formula (I):

wherein:

is one or more rings selected from the group consisting of:

R 1 is selected from the group consisting of —CO 2 R 10 and —CONR 10 SO 2 R 6 ;
R 2 is —CH═CH 2 ;
R 3 is C 1 -C 6 alkyl;
R 6 is C 3 cycloalkyl;
Y is selected from the group consisting of —OC(O)—;
Z is a direct bond;
M is selected from the group consisting of C 1 -C 12 alkylenes and C 2 -C 12 alkenylenes, wherein said M is substituted with 1 to 2 substituents F independently selected from the group consisting of C 1 -C 8 alkyl and ═CH 2 ;
X is selected from the group consisting of —(CH 2 ) 0-3 O—, wherein is attached to —(CH 2 ) 0-3 if present; and
each R 10 is independently H.

2. The compound according to claim 1 , wherein M is selected from the group consisting of —CH═CH(CH 2 ) 5 , —(CH 2 ) 7 —, —CH 2 CH═CH(CH 2 ) 4 —, —(CH 2 ) 6 —, —CH═CH(CH 2 ) 4 —, —CH═CH(CH 2 ) 3 C(CH 3 ) 2 CH 2 —, —CH═CH(CH 2 ) 3 —, —(CH 2 ) 5 —, —CH═CH(CH 2 ) 3 —, —(CH 2 ) 4 —, —(CH 2 ) 3 —, —CH═CH(CH 2 ) 2 C(CH 3 ) 2 CH 2 —, —(CH 2 ) 4 C(CH 3 ) 2 CH 2 —, —C(═CH 2 )(CH 2 ) 5 —, —C(═CH 2 )(CH 2 ) 3 —, and —CH 2 CH═CH(CH 2 ) 3 —.

3. The compound according to claim 2 , wherein M is selected from the group consisting of

4. A compound selected from the group consisting of:

5. A pharmaceutical composition comprising an effective amount of the compound according to claim 1 , and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition according to claim 5 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents, immunomodulators, and anti-infective agents.

7. The pharmaceutical composition according to claim 5 , further comprising a second therapeutic agent selected from the group consisting of HCV protease inhibitors and HCV NS5B polymerase inhibitors.

Assignees

• Merck Sharp & Dohme
• Msd Italia Srl

Inventors

• Liverton Nigel J
• Summa Vincenzo
• Harper Steven
• Mccauley John A
• Romano Joseph J
• Rudd Michael T

Classifications

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• C07K5/0804

  and aliphatic · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07D498/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title