Potent nonpeptide GnRH receptor antagonists derived from substituted indole-5-carboxamides and -acetamides bearing a pyridine side-chain terminus.
A pyridine side-chain terminus has been incorporated into the indole-5-carboxamide and indole-5-acetamide series of GnRH antagonists. Potent activity was observed in binding and functional assays. Certain branched or cyclic tertiary amides were identified as preferred in each series. Alkylation of the side-chain secondary amine had generally unfavorable effects. Variations of the gem-dialkyl substituents in the indole-5-acetamide series were also investigated.
Ashton
W T
WT
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 07065-0900, Rahway, NJ, USA. wally_ashton@merck.com
Sisco
R M
RM
Yang
Y T
YT
Lo
J L
JL
Yudkovitz
J B
JB
Gibbons
P H
PH
Mount
G R
GR
Ren
R N
RN
Butler
B S
BS
Cheng
K
K
Goulet
M T
MT
D000577:Amides / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*
D000577:Amides; D007211:Indoles; D011725:Pyridines; D011966:Receptors, LHRH; C023666:pyridine