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

Abstract 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 (R 3 , R 5 , R 5′ , and R 8 ) was investigated. By derivatization, three compounds ( 6 , 14b , and 14c) were identified as orally active CRF 1 receptor antagonists.