Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-12-06
1999-10-05
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
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Patent
active
059624795
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to pyridines, pyrimidines, purinones, pyrrolopyrimidinones and pyrrolopyridinones, processes for preparing them, pharmaceutical compositions containing them, and methods of using them to treat certain central nervous system (CNS) and other disorders.
CRF antagonists are mentioned in U.S. Pat. Nos. 4,605,642 and 5,063,245 referring to peptides and pyrazolinones, respectively. The importance of CRF antagonists is set out in the literature, e.g., as discussed in U.S. Pat. No. 5,063,245, which is incorporated herein by reference. A recent outline of the different activities possessed by CRF antagonists is found in M. J. Owens et al., Pharm. Rev., Vol. 43, pages 425 to 473 (1991), also incorporated herein by reference. Based on the research described in these two and other references, CRF antagonists are effective in the treatment of a wide range of stress-related illnesses, such as depression, anxiety, headache, irritable bowel syndrome, inflammatory diseases, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, hemorrhagic stress, drug and alcohol withdrawal symptoms, drug addiction, infertility, head trauma, stroke, and stress-induced infections in humans and animals.
SUMMARY OF THE INVENTION
The present invention relates to a compound of the formula ##STR2## or a pharmaceutically acceptable salt thereof, wherein the dashed lines represent optional double bonds; R.sub.12)R.sub.1, --NHCHR.sub.1 R.sub.2, --OCHR.sub.1 R.sub.2, --SCHR.sub.1 R.sub.2, --CHR.sub.2 OR.sub.12, --CHR.sub.2 SR.sub.12, --C(S)R.sub.2 or --C(O)R.sub.2 ; trifluoromethoxy, methyl, ethyl, thiomethoxy, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 or trifluoromethyl; wherein R.sub.13 and R.sub.14 are each, independently, hydrogen, trifluoromethyl or methyl, or one of R.sub.13 and R.sub.14 is cyano and the other is hydrogen or methyl; one or two substituents R.sub.8 independently selected from the group consisting of hydroxy, fluoro, chloro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.4 alkoxy, --O--CO--(C.sub.1 -C.sub.4 alkyl), --O--CO--NH(C.sub.1 -C.sub.4 alkyl), --O--CO--N(C.sub.1 -C.sub.4 alkyl)(C.sub.1 -C.sub.2 alkyl), --NH(C.sub.1 -C.sub.4 alkyl), --N(C.sub.1 -C.sub.2 alkyl)(C.sub.1 -C.sub.4 alkyl), --S(C.sub.1 -C.sub.4 alkyl), --N(C.sub.1 -C.sub.4 alkyl)CO(C.sub.1 -C.sub.4 alkyl), --NHCO(C.sub.1 -C.sub.4 alkyl), --COO(C.sub.1 -C.sub.4 alkyl), --CONH(C.sub.1 -C.sub.4 alkyl), --CON(C.sub.1 -C.sub.4 alkyl)(C.sub.1 -C.sub.2 alkyl), CN, NO.sub.2, --SO(C.sub.1 -C.sub.4 alkyl) and --SO.sub.2 (C.sub.1 -C.sub.4 alkyl), and wherein said C.sub.1 -C.sub.6 alkyl and the (C.sub.1 -C.sub.4)alkyl moieties in the foregoing R.sub.1 groups may optionally contain one carbon-carbon double or triple bond; alkylene)aryl wherein said aryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl, or benzoxazolyl; 3- to 8-membered cycloalkyl or --(C.sub.1 -C.sub.6 alkylene)cycloalkyl, wherein one or two of the ring carbons of said cycloalkyl having at least 4 ring members and the cycloalkyl moiety of said --(C.sub.1 -C.sub.6 alkylene)cycloalkyl having at least 4 ring members may optionally be replaced by an oxygen or sulfur atom or by N--R.sub.9 wherein R.sub.9 is hydrogen or C.sub.1 -C.sub.4 alkyl; and wherein each of the foregoing R.sub.2 groups may optionally be substituted with from one to three substituents independently selected from chloro, fluoro and C.sub.1 -C.sub.4 alkyl, or with one substituent selected from bromo, iodo, C.sub.1 -C.sub.6 alkoxy, --O--CO--(C.sub.1 -C.sub.6 alkyl), --O--CO--N(C.sub.1 -C.sub.4 alkyl)(C.sub.1 -C.sub.2 alkyl), --S(C.sub.1 -C.sub.6 alkyl), CN, NO.sub.2, --SO(C.sub.1 -C.sub.4 alkyl), and --SO.sub.2 (C.sub.1 -C.sub.4 alkyl), and wherein said C.sub.1 -C.sub.12 alkyl and the C.sub.1 -C.sub.4 alkylene moiety of said --(C.sub.1 -C.sub.4 alkylene)aryl may optionally contain one carbon-carbon double or triple
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Coleman Brenda
Ginsburg Paul H.
Konstas Kristina L.
Pfizer Inc.
Richardson Peter C.
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