title: Synthesis and SAR of 8-arylquinolines as potent corticotropin-releasing factor1 (CRF1) receptor antagonists.
abstract: A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF(1) receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[1,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF(1) antagonists with lower lipophilicity.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Centre Drive, San Diego, CA 92121, USA.
authors.forename: Charles Q
authors.initials: CQ
authors.lastname: Huang
authors.forename: Keith
authors.initials: K
authors.lastname: Wilcoxen
authors.forename: James R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: Mustapha
authors.initials: M
authors.lastname: Haddach
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Webb
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Xie
authors.forename: Dimitri E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; 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