US2007249629A1PendingUtilityA1
Viral Polymerase Inhibitors
Est. expiryJul 16, 2024(expired)· nominal 20-yr term from priority
Inventors:Pierre Louis BeaulieuChristian BrochuStephen KawaiJean RancourtTimothy A. StammersBounkham ThavonekhamYoula S. Tsantrizos
A61P 31/12A61P 31/14A61P 43/00A61P 1/16C07D 405/14C07D 409/04C07D 401/14C07D 209/08C07D 405/04C07D 417/04C07D 209/12C07D 403/04C07D 401/04C07D 209/42
54
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Claims
Abstract
A compound, represented by formula (I): wherein A, B, R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 9 , and R 10 are as defined herein, or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof, as an inhibitor of HCV NS5B polymerase.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
Wherein:
either A or B is N and the other B or A is C, wherein ----- between two C-atoms represents a double bond and ----- between a C-atom and a N-atom represents a single bond;
R 1 is H or (C 1-6 )alkyl;
R 2 is (C 1-6 )alkyl, (C 2-6 )alkynyl, —C(═O)—(C 1-6 )alkyl, aryl or Het; the aryl and Het being optionally substituted with R 21 ;
wherein R 21 is one two or three substituents each independently selected from (C 1-6 )alkyl, (C 3-7 )cycloalkyl, Het, —CN, —NH 2 , —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 , halo, —O—(C 1-6 )alkyl —S—(C 1-6 )alkyl —SO—(C 1-6 )alkyl and —SO 2 —(C 1-6 )alkyl;
wherein the (C 1-6 )alkyl, —O—(C 1-6 )alkyl, —S—(C 1-6 )alkyl, —SO—(C 1-6 )alkyl and —SO 2 —(C 1-6 )alkyl are each optionally substituted with one, two or three halo substituents;
R 3 is (C 5-6 )cycloalkyl optionally substituted with from one to four halo substituents;
R 5 is selected from H, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, Het and Het-(C 1-6 )alkyl-;
wherein the (C 1-6 )alkyl is optionally substituted with from one to three substituents each independently selected from halo, cyano, (C 1-6 )alkoxy, —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and —NHSO 2 (C 1-6 )alkyl;
and wherein each of the Het and the Het portion of the Het-(C 1-6 )alkyl- is optionally substituted with (C 1-6 )alkyl; and
R 6 is selected from H, (C 1-6 )alkyl and halo; or
R 5 and R 6 are linked such that the group of the subformula
is a group of formula wherein n is 0, 1 or 2; and wherein R 50 is selected independently in each instance from H, halo, cyano, (C 1-6 )alkoxy, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, Het and Het-(C 1-6 )alkyl-;
wherein the (C 1-6 )alkyl is optionally substituted with from one to three substituents each independently selected from halo, cyano, (C 1-6 )alkoxy, —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and —NHSO 2 (C 1-6 )alkyl; and wherein each of the Het and the Het portion of the Het-(C 1-6 )alkyl- is optionally substituted with (C 1-6 )alkyl;
R 7 is selected from H, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 1-6 )alkylthio, —NH 2 , —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and halo;
R 9 and R 10 are each independently selected from (C 1-6 )alkyl; or R 9 and R 10 are covalently bonded together to form (C 3-7 )cycloalkyl, (C 5-7 )cycloalkenyl or a 4-, 5- or 6-membered heterocycle having from 1 to 3 heteroatoms each independently selected from O, N, and S;
wherein the cycloalkyl, cycloalkenyl or heterocycle is optionally substituted with (C 1-4 )alkyl;
wherein Het is defined as a 4- to 7-membered heterocycle having 1 to 4 heteroatoms each independently selected from O, N and S, which may be saturated, unsaturated or aromatic, and which is optionally fused to at least one other cycle to form a 7 to 14-membered heteropolycycle having wherever possible 1 to 5 heteroatoms, each independently selected from O, N and S, the heteropolycycle being saturated, unsaturated or aromatic;
or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof.
2 . A compound of the following general formula
wherein R 2 , R 5 , R 9 and R 10 are given in the following table:
R 2
R 3
R 5
CH 3
CH 3
CH 3
CH 3
H
CH 3
CH 3
CH 3
CH 3
CH 3
or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof.
3 . A compound of the following general formula
wherein R 2 , R 3 , R 5 , R 6 , R 9 , and R 10 are given in the following table:
R 2
R 3
R 5
R 6
H
CH 3
H
H
CH 3
CH 3
CH 3
CH 3
H
H
H
F
H
H
H
H
H
H
CH 3
H
H
H
H
H
H
H
H
H
H
H
F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof.
4 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier.
5 . The pharmaceutical composition according to claim 1 additionally comprising a therapeutically effective amount of one or more other antiviral agents.
6 . A method of inhibiting the RNA-dependent RNA polymerase activity of the enzyme NS5B, encoded by HCV, comprising exposing the enzyme NS5B to an effective amount of a compound according to claim 1 under conditions where the RNA-dependent RNA polymerase activity of the enzyme NS5B is inhibited.
7 . A method of inhibiting HCV replication, comprising exposing a cell infected with HCV to an effective amount of a compound according to claim 1 under conditions where replication of HCV is inhibited.
8 . A method of treating or preventing HCV infection in a mammal, comprising administering to the mammal an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof.
9 . A method of treating or preventing HCV infection in a mammal, comprising administering to the mammal an effective amount of a combination of a compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, and at least one other antiviral agent.
10 . An article of manufacture comprising
a composition effective to treat an HCV infection; and packaging material comprising a label which indicates that the composition can be used to treat infection by the hepatitis C virus, wherein said composition comprises a compound according to claim 1 or a pharmaceutically acceptable salt or ester thereof.Cited by (0)
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