677761-35-2Relevant academic research and scientific papers
Design, synthesis, and structure-activity relationships of novel pyrazolo[5,1-b]thiazole derivatives as potent and orally active corticotropin-releasing factor 1 receptor antagonists
Takahashi, Yoshinori,Hashizume, Minako,Shin, Kogyoku,Terauchi, Taro,Takeda, Kunitoshi,Yonaga, Masahiro,Shikata, Kodo,Taguchi, Ryota,Ino, Mitsuhiro,Shibata, Hisashi,Murata-Tai, Kaoru,Fujisawa, Masae,Hibi, Shigeki
, p. 8450 - 8463,14 (2020/09/15)
This paper describes the design, synthesis, and structure-activity relationships of a novel series of 7-dialkylamino-3-phenyl-6-methoxy pyrazolo[5,1-b]thiazole derivatives for use as selective antagonists of the corticotropin-releasing factor 1 (CRF1) receptor. The most promising compound, N-butyl-3-[4-(ethoxymethyl)-2,6-dimethoxyphenyl]-6-methoxy-N- (tetrahydro-2H-pyran-4-yl)pyrazolo[5,1-b][1,3]thiazole-7-amine (6t), showed high affinity (IC50 = 70 nM) and functional antagonism (IC50 = 7.1 nM) for the human CRF1 receptor as well as dose-dependent inhibition of the CRF-induced increase in the plasma adrenocorticotropic hormone (ACTH) concentration at a dose of 30 mg/kg (po). Further, in the light/dark test in mice, the compound 6t showed anxiolytic activity at a dose of 30 mg/kg (po).
PYRAZOLOTHIAZOLE COMPOUND
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Page/Page column 33; 34, (2011/04/25)
A compound represented by the formula (I) or pharmacologically acceptable salt thereof exhibits an excellent CRF receptor antagonism wherein X is a nitrogen atom or CH; R1 is -A11-A12; A11 is a single bond or a C1-6 alkylene group; A12 is a hydrogen atom, a C1-6 alkyl group or a C3-6 cycloalkyl group, etc.; R2 is -A21-A22; A21 is a single bond or a C1-6 alkylene group; A22 is a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, a non-aromatic heterocyclic group, or a heteroaryl group, etc.; R3 is a C 1-6 alkyl group, a C3-6 cycloalkyl group, a C1-6 alkoxy group, a C3-6 cycloalkoxy C1-6 alkyl group, di-C1-6 alkyl amino group, a halogen atom, a cyano group, a formyl group, or a carboxyl group, etc; R4 is a hydrogen atom or a C1-6 alkoxy group; R5 is a halogen atom, a C1-6 alkyl group, or a C1-6 alkoxy group; R6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, or a C1-6 alkyl sulfinyl group etc.; and R7 is a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkylthio group
