1395411-82-1Relevant articles and documents
Design, synthesis, and structure-activity relationships of a series of 2-Ar-8-methyl-5-alkylaminoquinolines as novel CRF1 receptor antagonists
Takeda, Kunitoshi,Terauchi, Taro,Hashizume, Minako,Shin, Kogyoku,Ino, Mitsuhiro,Shibata, Hisashi,Yonaga, Masahiro
scheme or table, p. 5372 - 5378 (2012/09/22)
We designed and synthesized a series of 2-Ar-8-methyl-5- alkylaminolquinolines as potent corticotropin-releasing factor 1 (CRF 1) receptor antagonists. The structure-activity relationships of substituents at each position (R3, R5, R 5′, and R8) was investigated. By derivatization, three compounds (6, 14b, and 14c) were identified as orally active CRF 1 receptor antagonists.
Synthesis and structure-activity relationships of 8-substituted-2-aryl-5- alkylaminoquinolines: Potent, orally active corticotropin-releasing factor-1 receptor antagonists
Takeda, Kunitoshi,Terauchi, Taro,Hashizume, Minako,Shikata, Kohdoh,Taguchi, Ryota,Murata-Tai, Kaoru,Fujisawa, Masae,Takahashi, Yoshinori,Shin, Kogyoku,Ino, Mitsuhiro,Shibata, Hisashi,Yonaga, Masahiro
, p. 6559 - 6578 (2013/01/15)
We previously reported a series of 8-methyl-2-aryl-5-alkylaminoquinolines as a novel class of corticotropin-releasing factor-1 (CRF1) receptor antagonists. A critical issue encountered for this series of compounds was low aqueous solubility at physiological pH (pH 7.4). To address this issue, derivatization at key sites (R2, R3, R5, R 5′, and R8) was performed and the relationships between structure and solubility were examined. As a result, it was revealed that introduction of a methoxy substituent at the C8 position had a positive impact on the solubility of the derivatives. Consequently, through in vivo and in vitro biological studies, compound 21d was identified as a potent, orally active CRF1 receptor antagonist with improved physicochemical properties.
