Design, synthesis, and SAR of 2-dialkylamino-4-arylpyrimidines as potent and selective corticotropin-releasing factor(1) (CRF(1)) receptor antagonists.
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.
Huang
Charles Q
CQ
Neurocrine Biosciences, Inc, 10555 Science Centre Drive, San Diego, CA 92121, USA. chuang@neurocrine.com
Grigoriadis
Dimitri E
DE
Liu
Zhengyu
Z
McCarthy
James R
JR
Ramphal
John
J
Webb
Thomas
T
Whitten
Jeffrey P
JP
Xie
Michael Y
MY
Chen
Chen
C
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
D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1