US 2009/0155210 A1Published application

Oximyl hcv serine protease inhibitors

AssigneeEnanta Pharmaceuticals, Inc.

InventorsYONGHUA GAI, Yat Sun Or, Zhe Wang

Life of this patent

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Abstract

The present invention discloses compounds of formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Claims27

Dependent claims

A compound represented by the formula I:

as well as the pharmaceutically acceptable salts, esters and prodrugs thereof, wherein:
R1 and R2 are independently selected from the group consisting of:
a) hydrogen;
b) aryl;
c) substituted aryl;
d) heteroaryl;
e) substituted heteroaryl;
f) heterocyclic or substituted heterocyclic;
g) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
h) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
i) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
j) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
k) -Q-R3, where Q is (CO), (CO)O, (CO)NR4, (SO), (SO2), (SO2)NR4;
and R3 and R4 are independently selected from the group consisting of:
(i) hydrogen;
(ii) aryl;
(iii) substituted aryl;
(iv) heteroaryl;
(v) substituted heteroaryl;
(vi) heterocyclic;
(vii) substituted heterocyclic;
(viii) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(ix) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(x) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
(xi) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
or R1 and R2 taken together with the carbon atom to which they are attached form a cyclic moiety selected from:
substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocyclic;
or
substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocyclic each fused with one or more group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloakenyl, and substituted cycloalkenyl;
G is -E-R3, where E is absent or E is O, CO, (CO)O, (CO)NH, NR5, NH(CO), NH(CO)NH, NH(SO2)NH or NHSO2;
A is selected from the group consisting of R5, (CO)R5, (CO)OR5, (CO)NHR5, SO2R5, (SO2)OR5 and SO2NHR5;
R5 is selected from the group consisting of:
a) hydrogen;
b) aryl;
c) substituted aryl;
d) heteroaryl;
e) substituted heteroaryl;
f) heterocyclic;
g) substituted heterocyclic;
h)-C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
i) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
j) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
k) substituted —C3-C12 cycloalkyl, or substituted-C3-C12 cycloalkenyl;
B is H or CH3;
L is selected from the group consisting of:
(1) hydrogen;
(2) aryl;
(3) substituted aryl;
(4) heteroaryl;
(5) substituted heteroaryl;
(6) heterocyclic;
(7) substituted heterocyclic;
(8) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(9) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(10) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
(11) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
Z1 and Z2 are independently selected from halogen;
preferably F, Cl and Br;
m=0, 1, 2 or 3;
n=1, 2 or 3 and
h=1, 2, or 3.

58 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/328,433Filed 4 Dec 2008
Priority: 5 Dec 2007
Published: 18 Jun 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 38/21
Cytokines; Lymphokines; Interferons: interferons [IFN]
C07D 207/12
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Application60/992,572Us provisional application · filed 5 Dec 2007
US 8,361,958 B2Related patent
US 2009/0155210 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound represented by the formula I:

as well as the pharmaceutically acceptable salts, esters and prodrugs thereof, wherein:
R1 and R2 are independently selected from the group consisting of:
a) hydrogen;
b) aryl;
c) substituted aryl;
d) heteroaryl;
e) substituted heteroaryl;
f) heterocyclic or substituted heterocyclic;
g) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
h) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
i) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
j) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
k) -Q-R3, where Q is (CO), (CO)O, (CO)NR4, (SO), (SO2), (SO2)NR4;
and R3 and R4 are independently selected from the group consisting of:
(i) hydrogen;
(ii) aryl;
(iii) substituted aryl;
(iv) heteroaryl;
(v) substituted heteroaryl;
(vi) heterocyclic;
(vii) substituted heterocyclic;
(viii) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(ix) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(x) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
(xi) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
or R1 and R2 taken together with the carbon atom to which they are attached form a cyclic moiety selected from:
substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocyclic;
or
substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocyclic each fused with one or more group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, cycloakenyl, and substituted cycloalkenyl;
G is -E-R3, where E is absent or E is O, CO, (CO)O, (CO)NH, NR5, NH(CO), NH(CO)NH, NH(SO2)NH or NHSO2;
A is selected from the group consisting of R5, (CO)R5, (CO)OR5, (CO)NHR5, SO2R5, (SO2)OR5 and SO2NHR5;
R5 is selected from the group consisting of:
a) hydrogen;
b) aryl;
c) substituted aryl;
d) heteroaryl;
e) substituted heteroaryl;
f) heterocyclic;
g) substituted heterocyclic;
h)-C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
i) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
j) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
k) substituted —C3-C12 cycloalkyl, or substituted-C3-C12 cycloalkenyl;
B is H or CH3;
L is selected from the group consisting of:
(1) hydrogen;
(2) aryl;
(3) substituted aryl;
(4) heteroaryl;
(5) substituted heteroaryl;
(6) heterocyclic;
(7) substituted heterocyclic;
(8) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(9) substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
(10) —C3-C12 cycloalkyl, or —C3-C12 cycloalkenyl;
(11) substituted —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkenyl;
Z1 and Z2 are independently selected from halogen;
preferably F, Cl and Br;
m=0, 1, 2 or 3;
n=1, 2 or 3 and
h=1, 2, or 3.

58 more elements

Facts

Application

12/328,433Filed 4 Dec 2008

Priority

5 Dec 2007

Published

18 Jun 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 38/21
Cytokines; Lymphokines; Interferons: interferons [IFN]
C07D 207/12
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links