Potent antagonists of gonadotropin releasing hormone receptors derived from quinolone-6-carboxamides.
SAR studies which focused upon the C-6 position of a recently described series of quinolone gonadotropin releasing hormone antagonists are reported. Synthetic access to diverse quinolone-6-carboxamides was achieved via the palladium-catalyzed amino-carbonylation reactions of iodide 4 with various amines. Amides related to 9y were especially potent, functional antagonists of rat and human GnRH receptors.
Walsh
T F
TF
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Toupence
R B
RB
Young
J R
JR
Huang
S X
SX
Ujjainwalla
F
F
DeVita
R J
RJ
Goulet
M T
MT
Wyvratt
M J
MJ
Fisher
M H
MH
Lo
J L
JL
Ren
N
N
Yudkovitz
J B
JB
Yang
Y T
YT
Cheng
K
K
Smith
R G
RG
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D010716:Phosphatidylinositols; D015363:Quinolones; D011966:Receptors, LHRH; D007986:Luteinizing Hormone