Design, synthesis, and structure-activity relationships of a series of 2-Ar-8-methyl-5-alkylaminoquinolines as novel CRF1 receptor antagonists

We designed and synthesized a series of 2-Ar-8-methyl-5-alkylaminolquinolines as potent corticotropin-releasing factor 1 (CRF1) receptor antagonists. The structure-activity relationships of substituents at each position (R3, R5, R5′, and R8) was investigated. By derivatization, three compounds (6, 14b, and 14c) were identified as orally active CRF1 receptor antagonists.