Substituted indole-5-carboxamides and -acetamides as potent nonpeptide GnRH receptor antagonists.
The 2-aryltryptamine class of GnRH receptor antagonists has been modified to incorporate carboxamide and acetamide substituents at the indole 5-position. With either a phenol or methanesulfonamide terminus on the N-aralkyl side chain, potent binding affinity to the GnRH receptor was achieved. A functional assay for GnRH antagonism was even more sensitive to structural modification and revealed a strong preference for branched tertiary amides.
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
Cheng
K
K
Goulet
M T
MT
D000577:Amides / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D007211:Indoles; D011966:Receptors, LHRH