Design and synthesis of substituted quinolines as novel and selective melanin concentrating hormone antagonists as anti-obesity agents

Namal C Warshakoon; Justin Sheville; Ritu Tiku Bhatt; Wei Ji; Jose L Mendez-Andino; Kenneth M Meyers; Nick Kim; John A Wos; Chrissy Mitchell; Jennifer L Paris; Beth B Pinney; Ofer Reizes; X Eric Hu

doi:10.1016/j.bmcl.2006.07.006

Design and synthesis of substituted quinolines as novel and selective melanin concentrating hormone antagonists as anti-obesity agents

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5207-11. doi: 10.1016/j.bmcl.2006.07.006. Epub 2006 Jul 25.

Authors

Namal C Warshakoon¹, Justin Sheville, Ritu Tiku Bhatt, Wei Ji, Jose L Mendez-Andino, Kenneth M Meyers, Nick Kim, John A Wos, Chrissy Mitchell, Jennifer L Paris, Beth B Pinney, Ofer Reizes, X Eric Hu

Affiliation

¹ Drug Discovery Division, Procter and Gamble Pharmaceuticals Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. [email protected]

PMID: 16870427
DOI: 10.1016/j.bmcl.2006.07.006

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.

MeSH terms

Anti-Obesity Agents / chemical synthesis*
Anti-Obesity Agents / pharmacology
Drug Design
Humans
Hypothalamic Hormones / antagonists & inhibitors*
Inhibitory Concentration 50
Ligands
Melanins / antagonists & inhibitors*
Pituitary Hormones / antagonists & inhibitors*
Pyrimidinones
Quinolines / chemical synthesis*
Quinolines / pharmacology*
Structure-Activity Relationship
Substrate Specificity

Substances

Anti-Obesity Agents
Hypothalamic Hormones
Ligands
Melanins
Pituitary Hormones
Pyrimidinones
Quinolines
melanin-concentrating hormone