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US 9,284,307 B2Granted
Macrocyclic serine protease inhibitors
AssigneeIdenix Pharmaceuticals, Inc.
InventorsChristophe Claude Parsy, Francois-Rene Alexandre, Frederic Leroy, Thierry Convard, Dominique Surleraux
Life of this patent
Estimating the term…
Abstract
Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.
Claims18
A compound of Formula Ia or Ib:
- or a single enantiomer, a racemic mixture, a mixture of diastereomers, or an isotopic variant thereof;
- or a pharmaceutically acceptable salt thereof;
- wherein:
- R5 is —NHS(O)2R8;
- wherein R8 is 1-methylcyclopropyl or 1-ethynylcyclopropyl;
- L is —O— or —OC(O)NH—;
- R6 is methoxy-fluoro-(isopropylthiazolyl)quinolinyl, methoxy-chloro-(isopropyl-thiazolyl)quinolinyl, methoxy-bromo-(isopropylthiazolyl)quinolinyl, methoxy-methyl-(isopropylthiazolyl)quinolinyl, dimethoxy-(isopropylthiazolyl)quinolinyl, difluoromethyl-chloro-(isopropylthiazolyl)quinolinyl, difluoromethyl-methyl-(isopropylthiazolyl)quinolinyl, trifluoromethyl-methyl-(isopropyl-thiazolyl)quinolinyl, methanesulfonamido-chloro-(isopropylthiazolyl)quinolinyl, methane-sulfonamido-methyl-(isopropylthiazolyl)quinolinyl, methoxy-fluoro-(trifluoromethylthiazolyl)-quinolinyl, methoxy-chloro-(trifluoro-methylthiazolyl)quinolinyl, methoxy-bromo-(trifluoromethylthiazolyl)quinolinyl, methoxy-methyl-(trifluoromethylthiazolyl)quinolinyl, dimethoxy-(trifluoromethylthiazolyl)quinolinyl, methanesulfonamido-methyl-(trifluoromethylthiazolyl)quinolinyl, methoxy-chloro-(ethenyl-thiazolyl)quinolinyl, methoxy-chloro-(ethynylthiazolyl)quinolinyl, methoxy-methyl-(ethynyl-thiazolyl)quinolinyl, methoxy-chloro-(cyanothiazolyl)quinolinyl, methoxy-chloro-(methyl-thiazolyl)quinolinyl, methoxy-chloro-(cyclopropylthiazolyl)quinolinyl, methoxy-chloro-(cyclobutylthiazolyl)quinolinyl, chloro-methoxy-(isopropyl-1H-pyrazolyl)quinolinyl, methyl-methoxy-(isopropyl-1H-pyrazolyl)quinolinyl, chloro-methoxy-(trifluoromethyl-1H-pyrazolyl)-quinolinyl, methyl-methoxy-(trifluoromethyl-1H-pyrazolyl)quinolinyl, methoxy-fluoro-(isopropylisoxazolyl)quinolinyl, methoxy-chloro-(isopropyl-isoxazolyl)quinolinyl, methoxy-bromo-(isopropylisoxazolyl)quinolinyl, methoxy-methyl-(isopropylisoxazolyl)quinolinyl, dimethoxy-(isopropylisoxazolyl)quinolinyl;
- and
- Q1 is —N(R17)—;
- wherein R17 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
- Q2 has the structure of:
- wherein:
- Y is a bond, —O—, —S—, —S(O)—, —S(O)2—, or —N(RY)—, wherein RY is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, —C(O)RYa, —C(O)ORYa, —C(O)NRYbRYc, —S(O)2NRYbRYc, or —S(O)2RYa;
- where each RYa, RYb, and RYc is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
- q is an integer of 0, 1, 2, 3, or 4;
- r is an integer of 0, 1, 2, 3, or 4;
- and
- m is an integer of 0 or 1;
- and n is an integer of 1 or 2;
- with the proviso that the sum of m and n is 2.
17 more elements
Dependencies are inferred from the claim text.