Design and synthesis of substituted quinolines as novel and selective melanin concentrating hormone antagonists as anti-obesity agents.
A novel series of substituted quinoline analogs were designed and synthesized as potent and selective melanin concentrating hormone (MCH) antagonists. These analogs show potent (nM) activity (12a-k) with a moderate selectivity. Conversely, the conformationally constrained thienopyrimidinone analogs (18a-g) showed improved activity in MCH-1R and selectivity over 5HT2C.
Warshakoon
Namal C
NC
Drug Discovery Division, Procter and Gamble Pharmaceuticals Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. Warshakoon.nc@pg.com
Sheville
Justin
J
Bhatt
Ritu Tiku
RT
Ji
Wei
W
Mendez-Andino
Jose L
JL
Meyers
Kenneth M
KM
Kim
Nick
N
Wos
John A
JA
Mitchell
Chrissy
C
Paris
Jennifer L
JL
Pinney
Beth B
BB
Reizes
Ofer
O
Hu
X Eric
XE
D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007028:Hypothalamic Hormones / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008543:Melanins / Q000037:antagonists & inhibitors*; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D019440:Anti-Obesity Agents; D007028:Hypothalamic Hormones; D008024:Ligands; D008543:Melanins; D010907:Pituitary Hormones; D011744:Pyrimidinones; D011804:Quinolines; C019463:melanin-concentrating hormone