IP Library Granted Patent US 8,153,800
Granted Patent B2
US 8,153,800 · App. 13/197,226 · Granted Apr 10, 2012

Macrocyclic inhibitors of hepatitis C virus

Assignees: Tibotec Pharmaceuticals Ltd.; Medivar AB
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Quick Facts
Patent No.
US 8,153,800
App. No.
13/197,226
Granted
Apr 10, 2012
Kind
B2
Abstract

Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is —OR 7 or —NH—SO 2 R 8 ; R 2 is hydrogen, and where X is C or CH, R 2 may also be C 1-6 alkyl; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, or C 3-7 cycloalkyl; R 4 is aryl or Het; n is 3, 4, 5, or 6; R 5 is halo, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, phenyl, or Het; R 6 is C 1-6 alkoxy or dimethylamino; R 7 is hydrogen; aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; R 8 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

Claims (9)

1. A process for the preparation of a compound of formula

comprising the ring closure and dehydration of a compound of formula

2. The process according to claim 1 wherein the compound of formula (35) is prepared by coupling a compound of formula

with a compound having the formula

3. The process according to claim 1 wherein the hydroxy function in the compound of formula (36) is converted to a leaving group.

4. The process according to claim 3 wherein the leaving group is a halogen or an arylsulfonyl group.

5. A compound of formula

6. A compound of formula

7. A compound of formula

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2015
From: JANSSEN R & D IRELAND
To: JANSSEN SCIENCES IRELAND UC
Reel/Frame 035496/0382 →
CHANGE OF NAME Recorded Apr 15, 2015
From: TIBOTEC PHARMACEUTICALS
To: JANSSEN R&D IRELAND
Reel/Frame 035439/0981 →
Priority Claims (3)
EP 05107074 · Jul 29, 2005 · regional
EP 05107417 · Aug 11, 2005 · regional
EP 06101280 · Feb 3, 2006 · regional
Continuity (2)
Division 11632102
Related Publication 20110295012A1 · Dec 1, 2011