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US 7,888,464 B2Granted
Hepatitis C virus inhibitors
AssigneeBristol-Myers Squibb Company
InventorsAlan Xiangdong Wang, Barbara Zhizhen Zheng, Stanley D'Andrea, Qian Zhao, Paul Michael Scola
Life of this patent
Estimating the term…
Abstract
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
Claims18
A compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- n is 1, 2, or 3;
- R1 is selected from hydroxy and —NHSO2R7;
- R2 is selected from hydrogen, alkenyl, alkyl, cyanoalkyl, cycloalkyl, and haloalkyl;
- R3 is selected from alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and heterocyclylalkyl;
- R4 is —OR8;
- R5 is selected from alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, arylalkyl, carboxyalkyl, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, haloalkoxyalkyl, haloalkyl, hydroxyalkyl, (NRaRb)alkyl, and (NRaRb)carbonylalkyl;
- R6 is selected from alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, cycloalkyloxycarbonyl, cycloalkyl, haloalkoxycarbonyl, haloalkyl, haloalkylcarbonyl, (NRaRb)carbonyl, and (NRaRb)sulfonyl;
- or
- R6 is selected from phenyl and a five- or six-membered partially or fully unsaturated ring optionally containing one, two, three, or four heteroatoms selected from nitrogen, oxygen, and sulfur;
- wherein each of the rings is optionally substituted with one, two, three, or four substitutents independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfanyl, carboxy, cyano, cycloalkyl, cycloalkyloxy, halo, haloalkyl, haloalkoxy, —NRgRh, (NRjRk)carbonyl, (NRjRk)sulfonyl, and oxo;
- R7 is selected from alkyl, aryl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and —NRcRd;
- R8 is selected from alkoxyalkyl, alkyl, alkylcarbonyl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkylcarbonyl, haloalkoxyalkyl, haloalkyl, (NReRf)carbonyl, and —P(O)(OR′)2;
- wherein Re and Rf are independently selected from hydrogen, alkyl, and arylalkyl;
- or Re and Rf, together with the nitrogen atom to which they are attached, form a five or six-membered monocyclic heterocyclic ring optionally containing one additional heteroatom selected from O, NRx, and S;
- wherein Rx is selected from hydrogen and alkyl;
- and wherein R′ is selected from hydrogen and alkyl;
- Ra and Rb are independently selected from hydrogen, alkoxy, alkoxyalkyl, alkyl, aryl, arylalkyl, cycloalkyl, haloalkoxyalkyl, haloalkyl, heterocyclyl, and heterocyclylalkyl;
- Rc and Rd are independently selected from alkoxy, alkyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and heterocyclylalkyl;
- or Rc and Rd together with the nitrogen atom to which they are attached form a five or six-membered monocyclic heterocyclic ring;
- Rg and Rh are independently selected from hydrogen, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, arylalkyl, and haloalkyl;
- and
- Rj and Rk are independently selected from hydrogen, alkyl, aryl, arylalkyl, and heterocyclyl;
- wherein the aryl, the aryl part of the arylalkyl, and the heterocyclyl are optionally substituted with one or two substituents independently selected from alkoxy, alkyl, and halo.
21 more elements
A compound of formula (II)
- or a pharmaceutically acceptable salt thereof, wherein
- n is 1, 2, or 3;
- R2 is selected from hydrogen, alkenyl, alkyl, cyanoalkyl, cycloalkyl, and haloalkyl;
- R3 is selected from alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and heterocyclylalkyl;
- R5 is selected from alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, arylalkyl, carboxyalkyl, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, haloalkoxyalkyl, haloalkyl, hydroxyalkyl, (NRaRb)alkyl, and (NRaRb)carbonylalkyl;
- R6 is selected from alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, cycloalkyloxycarbonyl, cycloalkyl, haloalkoxycarbonyl, haloalkyl, haloalkylcarbonyl, (NRaRb)carbonyl, and (NRaRb)sulfonyl;
- or
- R6 is selected from phenyl and a five- or six-membered partially or fully unsaturated ring optionally containing one, two, three, or four heteroatoms selected from nitrogen, oxygen, and sulfur;
- wherein each of the rings is optionally substituted with one, two, three, or four substitutents independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfanyl, carboxy, cyano, cycloalkyl, cycloalkyloxy, halo, haloalkyl, haloalkoxy, —NRgRh, (NRjRk)carbonyl, (NRjRk)sulfonyl, and oxo;
- R7 is selected from alkyl, aryl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and —NRcRd;
- R8 is selected from alkoxyalkyl, alkyl, alkylcarbonyl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkylcarbonyl, haloalkoxyalkyl, haloalkyl, (NReRf)carbonyl, and —P(O)(OR′)2;
- wherein Re and Rf are independently selected from hydrogen, alkyl, and arylalkyl;
- or Re and Rf, together with the nitrogen atom to which they are attached, form a five or six-membered monocyclic heterocyclic ring optionally containing one additional heteroatom selected from O, NRx, and S;
- wherein Rx is selected from hydrogen and alkyl;
- and wherein R′ is selected from hydrogen and alkyl;
- Ra and Rb are independently selected from hydrogen, alkoxy, alkoxyalkyl, alkyl, aryl, arylalkyl, cycloalkyl, haloalkoxyalkyl, haloalkyl, heterocyclyl, and heterocyclylalkyl;
- Rc and Rd are independently selected from alkoxy, alkyl, aryl, arylalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclyl, and heterocyclylalkyl;
- or Rc and Rd together with the nitrogen atom to which they are attached form a five or six-membered monocyclic heterocyclic ring;
- Rg and Rh are independently selected from hydrogen, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, arylalkyl, and haloalkyl;
- and
- Rj and Rk are independently selected from hydrogen, alkyl, aryl, arylalkyl, and heterocyclyl;
- wherein the aryl, the aryl part of the arylalkyl, and the heterocyclyl are optionally substituted with one or two substituents independently selected from alkoxy, alkyl, and halo.
19 more elements
A compound selected from
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.