Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor antagonists.
A series of heterocyclic 2-(3,5-dimethylphenyl)tryptamine derivatives was prepared and evaluated on a rat gonadotropin releasing hormone receptor assay. The carbon tether length and heterocyclic ring attached to the amino group of 2-(3,5-dimethylphenyl)tryptamine were varied. Several of these derivatives were potent GnRH antagonists with the most potent compound having an IC50 of 16 nM.
Lin
P
P
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. peter_lin@merck.com
Parikh
M
M
Lo
J L
JL
Yang
Y T
YT
Cheng
K
K
Smith
R G
RG
Fisher
M H
MH
Wyvratt
M J
MJ
Goulet
M T
MT
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D015195:Drug Design; D005260:Female; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D006727:Hormone Antagonists / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D051381:Rats; D011966:Receptors, LHRH / Q000378:metabolism*; D014363:Tryptamines / Q000138:chemical synthesis* / Q000378:metabolism*
D006571:Heterocyclic Compounds; D006727:Hormone Antagonists; D011966:Receptors, LHRH; D014363:Tryptamines; C030820:tryptamine