title: Design and synthesis of substituted quinolines as novel and selective melanin concentrating hormone antagonists as anti-obesity agents.
abstract: 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.
authors.affiliation: Drug Discovery Division, Procter and Gamble Pharmaceuticals Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. Warshakoon.nc@pg.com
authors.forename: Namal C
authors.initials: NC
authors.lastname: Warshakoon
authors.forename: Justin
authors.initials: J
authors.lastname: Sheville
authors.forename: Ritu Tiku
authors.initials: RT
authors.lastname: Bhatt
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Jose L
authors.initials: JL
authors.lastname: Mendez-Andino
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Meyers
authors.forename: Nick
authors.initials: N
authors.lastname: Kim
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
authors.forename: Chrissy
authors.initials: C
authors.lastname: Mitchell
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Paris
authors.forename: Beth B
authors.initials: BB
authors.lastname: Pinney
authors.forename: Ofer
authors.initials: O
authors.lastname: Reizes
authors.forename: X Eric
authors.initials: XE
authors.lastname: Hu
mesh_terms: 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
chemical_list: D019440:Anti-Obesity Agents; D007028:Hypothalamic Hormones; D008024:Ligands; D008543:Melanins; D010907:Pituitary Hormones; D011744:Pyrimidinones; D011804:Quinolines; C019463:melanin-concentrating hormone