1401964-92-8Relevant articles and documents
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).