title: 6,7-Dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives as novel corticotropin-releasing factor 1 receptor antagonists.
abstract: To identify an orally active corticotropin-releasing factor 1 receptor antagonist, a series of 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives were designed, synthesized and evaluated. An in vitro study followed by in vivo and pharmacokinetic studies of these heterotricyclic compounds led us to the discovery of an orally active CRF1 receptor antagonist. The results of a structure-activity relationship study are presented.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. te.saitou@ono.co.jp
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Saito
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Obitsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Nagao
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kusumi
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumura
authors.forename: Sonoko
authors.initials: S
authors.lastname: Ueno
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishi
authors.forename: Seishi
authors.initials: S
authors.lastname: Katsumata
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kagamiishi
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone