title: 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.
authors.affiliation: Medicinal Chemistry, Tsukuba Research Laboratories, Eisai Co., Ltd, 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan. k5-takeda@hhc.eisai.co.jp
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Taro
authors.initials: T
authors.lastname: Terauchi
authors.forename: Minako
authors.initials: M
authors.lastname: Hashizume
authors.forename: Kogyoku
authors.initials: K
authors.lastname: Shin
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ino
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shibata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yonaga
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003863:Depression / Q000188:drug therapy; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D011804:Quinolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
chemical_list: D011804:Quinolines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1