IP Library Granted Patent US 8,754,105
Granted Patent B2
US 8,754,105 · App. 13/109,395 · Granted Jun 17, 2014

Macrocyclic inhibitors of hepatitis C virus

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Quick Facts
Patent No.
US 8,754,105
App. No.
13/109,395
Granted
Jun 17, 2014
Kind
B2
Abstract

Inhibitors of HCV replication of formula (I) the N-oxides, salts, and stereochemically isomeric forms thereof, wherein each dashed line (represented by ) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted on any carbon or nitrogen ring atom with one, two, three, or four substituents; L is a direct bond, —O—, —O—C 1-4 alkanediyl-, —O—C(═O)—, —O—C(═O)—NR 4a — or —O—C(═O)—NR 4a C 1-4 alkanediyl-; R 2 is hydrogen, —OR 5 , —C(═O)OR 5 , —C(═O)R 6 , —C(═O)NR 4a R 4b , —C(═O)NHR 4c , —NR 4a R 4b , —NHR 4c , —NR 4a SO p NR 4a R 4b , —NR 4a SO p R 7 , or B(OR 5 ) 2 ; R 3 is hydrogen, and where X is C or CH, R 3 may also be C 1-6 alkyl; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be 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 each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be 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 (6)

1. A compound having the following formula:

wherein n is 4 or 5;

R 2 is —NHS(═O) 2 R 7 , where R 7 is methyl, cyclopropyl, methylcyclopropyl, or phenyl;

and R 1 is a 9-12 membered bicyclic hetereocyclic ring having one N-hetereo atom, and having two substituents which are phenyl and lower alkoxy.

2. The compound of claim 1 in which R 1 is

3. A compound of claim 1 which is

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2015
From: JANSSEN R & D IRELAND
To: JANSSEN SCIENCES IRELAND UC
Reel/Frame 035496/0382 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2014
From: NILSSON, KARL MAGNUS; SAMUELSSON, BENGT BERTIL; ROSENQUIST, ASA ANNICA KRISTINA; ANTONOV, DMITRY
To: MEDIVIR AB
Reel/Frame 032091/0098 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2014
From: SIMMEN, KENNETH ALAN; DE KOCK, HERMAN AUGUSTINUS; RABOISSON, PIERRE JEAN-MARIE BERNARD; TAHRI, ABDELLAH
To: TIBOTEC BVBA
Reel/Frame 032091/0483 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2014
From: TIBOTEC BVBA
To: TIBOTEC PHARMACEUTICALS LTD.
Reel/Frame 032091/0917 →
CHANGE OF NAME Recorded Jan 30, 2014
From: TIBOTEC PHARMACEUTICALS
To: JANSSEN R&D IRELAND
Reel/Frame 032092/0094 →