The efficacy and cardiac evaluation of aminomethyl tetrahydronaphthalene ketopiperazines: a novel class of potent MCH-R1 antagonists.
The design, synthesis, and biological studies of a novel class of MCH-R1 antagonists based on an aminotetrahydronaphthalene ketopiperazine scaffold is described. Compounds within this class promoted significant body weight reduction in mouse diet induced obesity studies. The potential for hERG blockage activity and QT interval studies in anesthetized dogs are discussed.
Méndez-Andino
José L
JL
Procter & Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, OH 45039, USA. mendezandino.jl@pg.com
Colson
Anny-Odile
AO
Meyers
Kenneth M
KM
Mitchell
Maria C
MC
Hodge
Karen
K
Howard
Jeremy M
JM
Kim
Nicholas
N
Ackley
David C
DC
Holbert
Jerry K
JK
Mittelstadt
Scott W
SW
Dowty
Martin E
ME
Obringer
Cindy M
CM
Suchanek
Paula
P
Reizes
Ofer
O
Hu
X Eric
XE
Wos
John A
JA
D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C103263:MCHR1 protein, human; D010879:Piperazines; D017481:Receptors, Somatostatin