Synthesis and SAR of 8-arylquinolines as potent corticotropin-releasing factor1 (CRF1) receptor antagonists.
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.
Huang
Charles Q
CQ
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Centre Drive, San Diego, CA 92121, USA.
Wilcoxen
Keith
K
McCarthy
James R
JR
Haddach
Mustapha
M
Webb
Thomas R
TR
Gu
Jian
J
Xie
Yun-Feng
YF
Grigoriadis
Dimitri E
DE
Chen
Chen
C
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
D011804:Quinolines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1