US2004266799A1PendingUtilityA1
CRF receptor antagonists and methods relating thereto
Est. expiryNov 3, 2020(expired)· nominal 20-yr term from priority
A61P 5/04A61P 43/00A61P 25/22A61P 25/24A61P 25/00A61P 1/00C07D 471/06C07D 471/16
52
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Claims
Abstract
CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke.
Claims
exact text as granted — not AI-modified1 . A compound having the following structure:
including stereoisomers and pharmaceutically acceptable salts thereof,
wherein:
represents —N═CH—, —NH—CH 2 — or —NH—(CH 2 ) 2 —;
X is N or CR 3 ;
R 1 is —CH(R 4 )(R 5 );
R 2 is C 1-6 alkyl;
R 3 is hydrogen or C 1-6 alkyl;
R 4 is hydrogen, C 1-6 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxyC 1-6 alkyl, or C 1-6 alkyloxyC 1-6 alkyl, and
R 5 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)methyl, Ar 1 CH 2 , C 3-6 alkenyl, C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, thienylmethyl, furanylmethyl, C 1-6 alkylthioC 1-6 alkyl, morpholinyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylC 1-6 alkyl, C 1-6 alkyl substituted with imidazolyl, or a radical of the formula -(C 1-6 alkanediyl)-O—CO—Ar 1 ,
or R 4 and R 5 taken together with the carbon atom to which they are bonded form a C 5-8 cycloalkyl optionally substituted with one or more substituents independently selected from C 1-6 alkyl;
Ar is phenyl substituted with 1, 2 or 3 substituents independently selected from halo, C 1-6 alkyl, trifluoromethyl, cyano, C 1-6 alkyloxy, benzyloxy, C 1-6 alkylthio, nitro, amino, and mono- or di(C 1-6 alkyl)amino; or an aromatic C 3-12 heterocycle optionally substituted with 1, 2 or 3 substituents independently selected from halo, C 1-6 alkyl, trifluoromethyl, hydroxy, cyano, C 1-6 alkyloxy, benzyloxy, C 1-6 alkylthio, nitro, amino, mono- or di(C 1-6 alkyl)amino, and piperidinyl; and
Ar 1 is phenyl, pyridinyl, or phenyl substituted with 1, 2 or 3 substituents independently selected from halo, C 1-6 alkyl, C 1-6 alkyloxy, di(C 1-6 alkyl)aminoC 1-6 alkyl, trifluoromethyl and C 1-6 alkyl substituted with morpholinyl.
2 . The compound of claim 1 having the structure:
3 . The compound of claim 1 having the structure:
4 . The compound of claim 1 having the structure:
5 . The compound of claim 1 having the structure:
6 . The compound of claim 1 having the structure:
7 . The compound of claim 1 having the structure:
8 . The compound of claim 1 wherein Ar is 2,4-dichlorophenyl.
9 . The compound of claim 1 wherein Ar is 2-chloro-4-methyl-phenyl.
10 . The compound of claim 1 wherein Ar is 2-methyl-4-chloro-phenyl.
11 . The compound of claim 1 wherein Ar is 2,4,6-trimethyl-phenyl.
12 . The compound of claim 1 wherein Ar is 2-chloro-4-methoxy-phenyl.
13 . The compound of claim 1 wherein Ar is 2-methyl-4-methoxy-phenyl.
14 . The compound of claim 1 wherein Ar is 2,4-dimethoxy-phenyl.
15 . The compound of claim 1 wherein Ar is 4-dimethylamino-2-methyl-3-pyridyl.
16 . The compound of claim 1 wherein Ar is 4-dimethylamino-6-methyl-3-pyridyl.
17 . The compound of claim 1 wherein Ar is 4-dimethylamino-3-pyridyl.
18 . The compound of claim 1 wherein R 1 is —CH(n-propyl) 2 .
19 . The compound of claim 1 wherein R 1 is —CH(n-propyl)(CH 2 OCH 3 ).
20 . The compound of claim 1 wherein R 1 is —CH(benzyl)(CH 2 OCH 3 ).
21 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR) 2 and each occurrence of R is independently selected from C 1-6 alkyl.
22 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR)(ethyl) and each occurrence of R is independently selected from C 1-6 alkyl.
23 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR)(n-butyl) and each occurrence of R is independently selected from C 1-6 alkyl.
24 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR)(tert-butyl) and each occurrence of R is independently selected from C 1-6 alkyl.
25 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR)(4-chloro-benzyl) and each occurrence of R is independently selected from C 1-6 alkyl.
26 . The compound of claim 1 wherein R 1 is —CH(CH 2 OR)(CH 2 CH 2 SCH 3 ) and each occurrence of R is independently selected from C 1-6 alkyl.
27 . The compound of claim 1 wherein R 1 —CH(CH 2 CH 3 )(CH 2 Obenzyl).
28 . The compound of claim 1 wherein R 2 is methyl.
29 . The compound of claim 1 wherein R 2 is ethyl.
30 . A pharmaceutical composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.
31 . A method for treating a disorder manifesting hypersecretion of CRF in a warm-blooded animal, comprising administering to the animal an effective amount of the pharmaceutical composition of claim 30 .
32 . The method of claim 31 wherein the disorder is stroke.
33 . The method of claim 31 wherein the disorder is anxiety.
34 . The method of claim 31 wherein the disorder is depression.
35 . The method of claim 31 wherein the disorder is irritable bowel syndrome.Join the waitlist — get patent alerts
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