Initial structure-activity relationship of a novel class of nonpeptidyl GnRH receptor antagonists: 2-arylindoles.
A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core, was identified through the Merck in-house screening for binding affinity on the rat GnRH receptor. SAR studies directed toward the alkoxy-ethanolamine and 2-aryl groups resulted in a simpler lead structure with improved activity. This compound 50 exhibits a 60-fold improvement in binding activity over our initial lead 1.
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. lin_chu@merck.com
L
L
Chu
J E
JE
Hutchins
A E
AE
Weber
J L
JL
Lo
Y T
YT
Yang
K
K
Cheng
R G
RG
Smith
M H
MH
Fisher
M J
MJ
Wyvratt
M T
MT
Goulet
D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D007211:Indoles; D011966:Receptors, LHRH