US2008064734A1PendingUtilityA1
Anilinopyrazole derivatives useful for the treatment of diabetes
Assignee: BAYER PHARMACEUTICALS CORPPriority: Nov 27, 2002Filed: Aug 31, 2007Published: Mar 13, 2008
Est. expiryNov 27, 2022(expired)· nominal 20-yr term from priority
Inventors:Joachim RudolphLouis-David CantinSteven R. MagnusonWilliam BullockAnn-Marie BullionLibing ChenChih-Yuan ChuangSidney LiangDyuti MajumdarHerbert OgutuAlan OlagueNing QiPhilip Wickens
A61P 3/10A61P 7/12A61P 5/50A61P 5/48A61P 3/06A61P 3/04A61P 3/00C07D 231/38C07D 413/12C07D 471/04C07D 401/04C07D 403/12
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Claims
Abstract
The present invention relates to anilinopyrazole compounds, pharmaceutical compositions, and methods for treating diabetes and related disorders.
Claims
exact text as granted — not AI-modified1 . A compound of Formula (I)
wherein
R is H or (C 1 -C 6 )alkyl;
R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )alkenyl,
(C 3 -C 6 )alkynyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo,
(C 1 -C 3 )haloalkyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 2 is H,
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo,
(C 1 -C 3 )haloalkyl,
pyridyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
pyrimidyl,
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
hydroxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio,
halo,
CO 2 R 8 ,
(C 1 -C 3 )haloalkoxy,
(C 1 -C 4 )acyl, and
benzoyl, or
tetrahydronaphthyl, indanyl, benzodioxolyl, or benzodioxanyl, each of which may be optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
or
when R 1 and R 2 are (C 1 -C 6 )alkyl, they may, together with C atoms to which they are attached, form a 5- or 6-membered carbocyclic ring,
or
R 1 and R 2 may, together with the C atoms to which they are attached form a 6-membered heterocyclic ring containing a N atom and optionally substituted on N with (C 1 -C 3 )alkyl;
R 3 is (C 1 -C 6 )alkyl,
(C 3 -C 6 )cycloalkyl,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 3 )haloalkyl,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio, and
SO 2 (C 1 -C 3 )alkyl,
(C 2 -C 3 )haloalkyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 3 )haloalkyl,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio, and
SO 2 (C 1 -C 3 )alkyl;
R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 6 )alkylthio,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
halo,
NR 8 R 8 ,
pyrimidyl,
pyridyl,
imidazolyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
n=0, 1, 2, or 3;
X is CO 2 R 8 , CONR 5 R 6 , SO 2 NHR 7 , or oxadiazolyl optionally substituted with (C 1 -C 6 )alkyl;
R 5 is H,
(C 1 -C 6 )alkyl,
(C 2 -C 6 )alkyl substituted with OR 6 ,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
pyridyl optionally substituted with up to two substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
SO 2 -phenyl said phenyl optionally substituted with up to four substituents selected from the group consisting of
halo
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 6 is H or (C 1 -C 6 )alkyl;
or
R 5 and R 6 together with N atom to which they are attached, may form a piperidine, morpholine, thiomorpholine, or piperazine ring said piperazine optionally substituted on N with (C 1 -C 3 )alkyl;
R 7 is H or methyl;
R 8 is H,
(C 1 -C 6 )alkyl,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 3 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio,
or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio;
and pharmaceutically acceptable salts thereof;
provided that when R and R 2 are H and X is CO 2 H, then R 1 is not H, methyl, or ethyl,
and further provided that the Formula (I) compound is not
2 . The compound of claim 1 , wherein
R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
and R, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .
3 . The compound of claim 1 , wherein
R 2 is pyridyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
hydroxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio,
halo,
CO 2 R 8 ,
(C 1 -C 3 )haloalkoxy,
(C 1 -C 4 )acyl, and
benzoyl;
and R, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .
4 . The compound of claim 1 , wherein
X is CO 2 R 8 ; and R, R 1 , R 2 , R 3 , R 4 , R 8 , and n are as defined in claim 1 .
5 . The compound of claim 1 , wherein
R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 2 is H,
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or
(C 1 -C 3 )haloalkyl;
and R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .
6 . The compound of claim 1 , wherein
R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )alkenyl,
(C 3 -C 6 )alkynyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or
(C 1 -C 3 )haloalkyl;
R 2 is H,
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or
(C 1 -C 3 )haloalkyl;
and R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .
7 . The compound of claim 1 , wherein
R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )alkenyl,
(C 3 -C 6 )alkynyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or
(C 1 -C 3 )haloalkyl;
R 2 is pyridyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
hydroxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio,
halo,
CO 2 R 8 ,
(C 1 -C 3 )haloalkoxy,
(C 1 -C 4 )acyl, and
benzoyl;
and R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .
8 . The compound of claim 1 , wherein
R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 2 is H,
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or
(C 1 -C 3 )haloalkyl;
X is CO 2 R 8 ; and R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .
9 . The compound of claim 1 , wherein
R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )alkenyl,
(C 3 -C 6 )alkynyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or
(C 1 -C 3 )haloalkyl;
R 2 is H,
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or
(C 1 -C 3 )haloalkyl;
X is CO 2 R 8 ; and R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .
10 . The compound of claim 1 , wherein
R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )alkenyl,
(C 3 -C 6 )alkynyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or
(C 1 -C 3 )haloalkyl;
R 2 is pyridyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
hydroxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio,
halo,
CO 2 R 8 ,
(C 1 -C 3 )haloalkoxy,
(C 1 -C 4 )acyl, and
benzoyl;
X is CO 2 R 8 ; and R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .
11 . The compound of claim 1 , wherein
R is H; R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,
(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo,
(C 1 -C 3 )haloalkyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 2 is H,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
pyridyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
hydroxy,
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio,
halo,
CO 2 R 8 ,
(C 1 -C 3 )haloalkoxy,
(C 1 -C 4 )acyl, and
benzoyl;
R 3 is (C 1 -C 6 )alkyl,
(C 3 -C 6 )cycloalkyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 3 )haloalkyl,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio, and
SO 2 (C 1 -C 3 )alkyl;
R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
halo,
phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
n=0, 1, 2, or 3; X is CO 2 R 8 ; and R 8 is H,
(C 1 -C 6 )alkyl,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 3 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio.
12 . The compound of claim 1 , wherein
R is H; R 1 is H,
(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl, or
phenyl optionally substituted with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 2 is H,
halo, or
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy;
R 3 is (C 1 -C 6 )alkyl,
or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 3 )haloalkyl,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy
NR 8 R 8 ,
cyano,
(C 1 -C 6 )alkylthio, and
SO 2 (C 1 -C 3 )alkyl;
R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 6 )alkylthio,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
halo;
n=0, 1, 2, or 3; X is CONR 5 R 6 ; R 5 is H,
(C 1 -C 6 )alkyl,
(C 2 -C 6 )alkyl substituted with OR 6 ,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
pyridyl optionally substituted with up to two substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio,
SO 2 -phenyl said phenyl optionally substituted with up to four substituents selected from the group consisting of
halo
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
NR 8 R 8 ,
cyano, and
(C 1 -C 6 )alkylthio;
R 6 is H or (C 1 -C 6 )alkyl;
or
R 5 and R 6 together with N atom to which they are attached, may form a piperidine, morpholine, thiomorpholine, or piperazine ring said piperazine optionally substituted on N with (C 1 -C 3 )alkyl; and R 8 is H,
(C 1 -C 6 )alkyl,
benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of
halo,
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
(C 1 -C 3 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio,
or
phenyl optionally substituted with up to four substituents selected from the group consisting of
(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,
halo,
(C 1 -C 6 )alkoxy,
(C 1 -C 3 )haloalkyl,
(C 1 -C 3 )haloalkoxy,
cyano, and
(C 1 -C 6 )alkylthio.
13 . The compound of claim 1 selected from the group consisting of
2-[(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid; 2-{[3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzamide; 2-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[3-tert-butyl-1-(2-methoxyphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-[(1,3-diphenyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid; 2-fluoro-6-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-fluoro-6-{[1-(2-methylphenyl)-3-(4-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(5-fluoro-2-methylphenyl)-1H-pyrazol-5-yl]amino}-6-fluorobenzoic acid; 2-({3-tert-butyl-1-[2-(methylthio)phenyl]-1H-pyrazol-5-yl}amino)-5-methoxybenzoic acid; 2-{[3-tert-butyl-1-(2-ethoxyphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(2-ethoxyphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 5-methoxy-2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methylbenzoic acid; 2-{[3-tert-butyl-1-(2-methoxyphenyl)-4-methyl-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-[(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid; 2-{[3-tert-butyl-1-(5-fluoro-2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(2,6-dimethylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(2-methoxy-5-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-tert-butyl-1-(2,3-dimethylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[3-tert-butyl-1-(2-methoxy-6-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[3-tert-butyl-1-(2,6-dimethylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[1-(2,6-dimethylphenyl)-3-(1-methylcyclopropyl)-1H-pyrazol-5-yl]amino}benzoic acid; 5) 2-{[1-(2,6-dimethylphenyl)-3-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 5-methoxy-2-{[3-methyl-1-(2-methylphenyl)-4-phenyl-1H-pyrazol-5-yl]amino}benzoic acid; 5-methoxy-2-{[4-(6-methoxypyridin-3-yl)-3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid; 5-methoxy-2-{[1-(2-methylphenyl)-4-pyridin-4-yl-3-(trifluoromethyl)-1H-pyrazol-5-yl]amino}benzoic acid; 5-methoxy-2-{[4-(4-methoxyphenyl)-1-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]amino}benzoic acid; 2-{[3-ethyl-4-(6-methoxypyridin-3-yl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 2-{[4-(2-fluorophenyl)-3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid; 5-methoxy-2-{[1-(2-methoxyphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-yl]amino}benzoic acid; and 2-{[4-(2,4-dimethoxyphenyl)-3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid.
14 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, in combination with a pharmaceutically acceptable carrier.
15 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents.
16 . The pharmaceutical composition of claim 15 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, anti-obesity agents, HMG CoA reductase inhibitors, nicotinic acid, bile acid sequestrants, fibric acid derivatives, and anti-hypertensive agents.
17 . A composition comprising an effective amount of a compound of claim 1 , or a salt thereof, in combination with an inert carrier.
18 . A method of treating diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
19 . The method of claim 18 , wherein said diabetes is selected from the group consisting of type 1 diabetes, type 2 diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes adult, and gestational diabetes.
20 . A method of treating Syndrome X comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
21 . A method of treating diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
22 . The method of claim 21 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.
23 . A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
24 . A method of treating cardiovascular diseases comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
25 . A method of treating diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.
26 . The method of claim 25 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.
27 . The method of claim 25 , wherein said diabetes is selected from the group consisting of type 1 diabetes, type 2 diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes adult, and gestational diabetes.
28 . A method of treating Syndrome X comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.
29 . The method of claim 28 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.
30 . A method of treating diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.
31 . The method of claim 30 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.
32 . The method of claim 30 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.
33 . A method of treating diabetes, Syndrome X, or diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more agents selected from the group consisting of HMG CoA reductase inhibitors, nicotinic acid, bile acid sequestrants, fibric acid derivatives, and anti-hypertensive agents.
34 . The method of claim 33 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.
35 . The method of any one of claims 25 to 34 , wherein the compound of claim 1 and one or more pharmaceutical agents are administered as a single pharmaceutical dosage formulation.
36 . A method of treating or preventing secondary causes of diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
37 . The method of claim 36 , wherein said secondary cause is selected from the group consisting of glucocorticoid excess, growth hormone excess, pheochromocytoma, and drug-induced diabetes.
38 . A method of treating or preventing secondary causes of diabetes comprising the step of administering a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.
39 . The method of claim 38 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.
40 . A method of stimulating insulin secretion in a subject in need thereof by administering to said subject a compound of claim 1 .
41 . Compounds according to claim 1 for the treatment and/or prophylaxis of diabetes and diabetes-related disorders.
42 . Medicament containing at least one compound according to claim 1 in combination with at least one pharmaceutically acceptable, pharmaceutically safe carrier or excipient.
43 . Use of compounds according to claim 1 for manufacturing a medicament for the treatment and/or prophylaxis of diabetes and diabetes-related disorders.
44 . Medicaments according to claim 42 for the treatment and/or prophylaxis of diabetes.
45 . A method of identifying a biological target comprising
contacting a compound of claim 1 with a biological sample; forming a complex with the compound and the biological target; isolating the compound-target complex; and identifying the target.
46 . The method of claim 45 , wherein the biological sample is pancreatic β-cells.
47 . The method of claim 45 , wherein the compound is labeled with a photoactive group and/or radioisotope.
48 . The method of claim 45 , wherein the compound is coupled to a polymer.Join the waitlist — get patent alerts
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