Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-12-03
1999-10-19
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514307, 514311, 514403, 546101, 546110, 546139, 546152, 5483647, A01N 4342, A01N 4356, C07D22106, C07D21700
Patent
active
059689447
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to substituted pyrazoles, pharmaceutical compositions containing them, and their use in the treatment of stress-related and other diseases. The compounds have corticotropin-releasing factor (CRF) antagonist activity.
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 considered effective in the treatment of a wide range of stress-related illnesses, such as stress-induced depression, anxiety, headache, irritable bowel syndrome, inflammatory diseases, immune suppression, human immunodeficiency virus (HIV) infections, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, hemorrhagic stress, drug and alcohol withdrawal symptoms, drug addiction, and fertility problems.
SUMMARY OF THE INVENTION
The present invention relates to a compound of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein -C.sub.6 alkyl containing one or two non-adjacent double bonds; hydroxy; O(C.sub.1 -C.sub.6 alkyl); SH; S(C.sub.1 -C.sub.6 alkyl); SO.sub.2 (C.sub.1 -C.sub.6 alkyl); C.sub.3 -C.sub.6 cycloalkyl; morpholinyl; piperidinyl, or aryl which aryl may be substituted by one to three of fluoro, chloro, bromo, trifluoromethyl, hydroxy, O(C.sub.1 -C.sub.6 alkyl), SH, S(C.sub.1 -C.sub.6 alkyl), amino, NH(C.sub.1 -C.sub.6 alkyl), N(C.sub.1 -C.sub.6 alkyl).sub.2, or one of iodo, nitro or cyano, said aryl being selected from the group consisting of phenyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinolyl, pyrimidyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzoisothiazolyl, isoxazolyl, benzisoxazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, azaindolyl, oxazolyl, benzoxazolyl, pyrrolidinyl, and thiazolidinyl; C.sub.3 -C.sub.8 alkenyl wherein the double bond is not adjacent to X.sub.1 when X.sub.1 is a heteroatom, or C.sub.3 -C.sub.7 cycloalkyl(CH.sub.2).sub.n wherein n is 0 to 4, or (CH.sub.2).sub.q Q.sub.1 R.sub.19 wherein q is 0, 1 or 2, Q.sub.1 is O, S, NH, N(C.sub.1 -C.sub.6 alkyl), or a covalent bond when X.sub.1 is not a covalent bond, and R.sub.19 is hydrogen, linear C.sub.1 -C.sub.6 alkyl, branched C.sub.3 -C.sub.8, C.sub.3 -C.sub.8 alkenyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.3 -C.sub.6 cycloalkyl (CH.sub.2); linear C.sub.1 -C.sub.6 alkyl or branched C.sub.3 -C.sub.8 alkyl; bromo, formyl, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.10 branched alkyl, C.sub.1 -C.sub.6 alkoxy or trifluoromethyl, or by one of hydroxy, iodo, cyano, nitro, amino, NH(C.sub.1 -C.sub.4 alkyl), N(C.sub.1 -C.sub.4)(C.sub.1 C.sub.2 alkyl), COO(C.sub.1 -C.sub.4 alkyl), CO(C.sub.1 -C.sub.4 alkyl), SO.sub.2 NH(C.sub.1 -C.sub.4 alkyl), SO.sub.2 N(C.sub.1 -C.sub.4 alkyl)(C.sub.1 -C.sub.2 alkyl), SO.sub.2 NH.sub.2, NHSO.sub.2 (C.sub.1 -C.sub.4 alkyl), S(C.sub.1 -C.sub.6 alkyl), SO.sub.2 (C.sub.1 -C.sub.6 alkyl), wherein said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.6 alkyl may be substituted by one or two of fluoro, chloro, hydroxy, C.sub.1 -C.sub.4 alkoxy, amino, methylamino, dimethylamino or acetyl wherein said C.sub.1 -C.sub.4 alkyl and C.sub.1 -C.sub.6 alkyl may contain one double or triple bond; thienyl, benzothienyl, pyridyl, quinolyl, pyrazinolyl, pyrimidyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, isoxazolyl, benzisoxazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, azaindolyl, oxazolyl, benzoxazolyl, pyrrolidinyl, thiazolidinyl, morpholinyl, or piperidinyl, each of which may be substituted by one to three of any one of fluoro, chlo
REFERENCES:
patent: 4081543 (1978-03-01), Bastian
patent: 5646152 (1997-07-01), Bright et al.
Bright Gene M
Welch, Jr. Willard M
Creagan B. Timothy
Ginsburg Paul H.
Ngo Tamthom T.
Pfizer Inc.
Richardson Peter C.
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