title: Design, synthesis, and SAR of 2-dialkylamino-4-arylpyrimidines as potent and selective corticotropin-releasing factor(1) (CRF(1)) receptor antagonists.
abstract: A series of 2-dialkylamino-4-phenylpyrimidines (7) was designed and synthesized as CRF(1) antagonists. SAR studies of this series resulted in the discovery of potent and selective antagonists 7b and 7n bearing a 4-(2,4,6-trisubstituted-phenyl) ring and a bulky 2-(N-bis(cyclopropane)methyl-N-propyl)amino group.
authors.affiliation: Neurocrine Biosciences, Inc, 10555 Science Centre Drive, San Diego, CA 92121, USA. chuang@neurocrine.com
authors.forename: Charles Q
authors.initials: CQ
authors.lastname: Huang
authors.forename: Dimitri E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Liu
authors.forename: James R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: John
authors.initials: J
authors.lastname: Ramphal
authors.forename: Thomas
authors.initials: T
authors.lastname: Webb
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Whitten
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Xie
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1