US2017128444A1PendingUtilityA1
Polycyclic-carbamoylpyridone compounds and their pharmaceutical use
Est. expiryJul 12, 2033(~7 yrs left)· nominal 20-yr term from priority
A61P 31/18A61P 31/00C07D 471/14A61K 31/4985C07D 471/18
60
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Claims
Abstract
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein L, R 5 , W, X, Y 1 , Y 2 , and Z are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating an HIV infection in a human having or at risk of having an HIV infection by administering to the human a therapeutically effective amount of a compound having the following Formula (I):
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein:
Y 1 and Y 2 are each, independently, hydrogen, C 1-3 alkyl or C 1-3 haloalkyl;
R 1 is phenyl substituted with one to three halogens;
X is —CHR 2 —;
W is a bond;
Z is —CHR 4 —;
R 2 and R 4 are each, independently, hydrogen or C 1-3 alkyl;
R 5 is hydrogen, C 1-3 alkyl or C 1-3 haloalkyl;
L is —C(R a ) 2 C(R a ) 2 C(R a ) 2 —; and
each R a is, independently, hydrogen, halo, hydroxy or C 1-4 alkyl.
2 - 6 . (canceled)
7 . The method of claim 1 wherein the compound of Formula I is represented by Formula (IV):
8 . The method of claim 7 wherein the compound of Formula I is represented by Formula (IV-A):
9 - 11 . (canceled)
12 . The method of claim 1 wherein each R a is hydrogen.
13 . The method of claim 1 wherein R 1 is substituted with one halogen.
14 . The method of claim 13 wherein R 1 is 4-fluorophenyl or 2-fluorophenyl.
15 . The method of claim 1 wherein R 1 is substituted with two halogens.
16 . The method of claim 15 wherein R 1 is 2,4-difluorophenyl, 2,3-difluorophenyl, 2,6-difluorophenyl, 3-fluoro-4-chlorophenyl, 3,4-difluorophenyl, 2-fluoro-4-chlorophenyl, or 3,5-difluorophenyl.
17 . The method of claim 15 wherein R 1 is 2,4-difluorophenyl, 2,3-difluorophenyl, 2,6-difluorophenyl, 3-fluoro-4-chlorophenyl, 3,4-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-4-chlorophenyl, or 3,5-difluorophenyl.
18 . The method of claim 16 wherein R 1 is 2,4-difluorophenyl.
19 . The method of claim 1 wherein R 1 is substituted with three halogens.
20 . The method of claim 19 wherein R 1 is 2,4,6-trifluorophenyl or 2,3,4-trifluorophenyl.
21 . The method of claim 20 wherein R 1 is 2,4,6-trifluorophenyl.
22 . The method of claim 1 wherein R 5 is hydrogen or C 1-3 alkyl.
23 . The method of claim 1 wherein R 5 is hydrogen.
24 . The method of claim 1 wherein R 5 is methyl.
25 . The method of claim 1 wherein the compound is selected from:
26 - 30 . (canceled)
31 . A method of inhibiting integrase activity in a human comprising administering to the human a therapeutically effective amount of a compound having the following Formula (I):
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein:
Y 1 and Y 2 are each, independently, hydrogen, C 1-3 alkyl or C 1-3 haloalkyl;
R 1 is phenyl substituted with one to three halogens;
X is —CHR 2 —;
W is a bond;
Z is —CHR 4 —;
R 2 and R 4 are each, independently, hydrogen or C 1-3 alkyl;
R 5 is hydrogen, C 1-3 alkyl or C 1-3 haloalkyl;
L is —C(R a ) 2 C(R a ) 2 C(R a ) 2 —; and
each R a is, independently, hydrogen, halo, hydroxy or C 1-4 alkyl.
32 . The method of claim 31 wherein the human is infected with human immunodeficiency virus.
33 . The method of claim 32 wherein the compound of Formula I is represented by Formula (IV):
34 . The method of claim 33 wherein the compound of Formula I is represented by Formula (IV-A):
35 . The method of claim 32 wherein each R a is hydrogen.
36 . The method of claim 32 wherein R 1 is substituted with one halogen.
37 . The method of claim 36 wherein R 1 is 4-fluorophenyl or 2-fluorophenyl.
38 . The method of claim 32 wherein R 1 is substituted with two halogens.
39 . The method of claim 38 wherein R 1 is 2,4-difluorophenyl, 2,3-difluorophenyl, 2,6-difluorophenyl, 3-fluoro-4-chlorophenyl, 3,4-difluorophenyl, 2-fluoro-4-chlorophenyl, or 3,5-difluorophenyl.
40 . The method of claim 38 wherein R 1 is 2,4-difluorophenyl, 2,3-difluorophenyl, 2,6-difluorophenyl, 3-fluoro-4-chlorophenyl, 3,4-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-4-chlorophenyl, or 3,5-difluorophenyl.
41 . The method of claim 39 wherein R 1 is 2,4-difluorophenyl.
42 . The method of claim 32 wherein R 1 is substituted with three halogens.
43 . The method of claim 42 wherein R 1 is 2,4,6-trifluorophenyl or 2,3,4-trifluorophenyl.
44 . The method of claim 43 wherein R 1 is 2,4,6-trifluorophenyl.
45 . The method of claim 32 wherein R 5 is hydrogen or C 1-3 alkyl.
46 . The method of claim 32 wherein R 5 is hydrogen.
47 . The method of claim 32 wherein R 5 is methyl.
48 . The method of claim 32 wherein the compound is selected from:Join the waitlist — get patent alerts
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