Melanin concentrating hormone receptor 1 (MCHR1) antagonists-Still a viable approach for obesity treatment?

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Hogberg, Thomas¹  Frimurer, Thomas M.²  Sasmal, Pradip K.³ 

[1] LEO Pharma, Chem Res, DK-2750 Ballerup, Denmark

[2] Univ Copenhagen, NNF Ctr Prot Res, DK-2200 Copenhagen, Denmark

[3] Dr Reddys Labs Ltd, Proprietary Prod, Hyderabad 500090, Andhra Pradesh, India

关键词: Melanin concentrating hormone (MCH);    MCHR1 antagonists;    Chemometric analysis;    GPCR structures;    hERG;    Obesity;   

DOI  :  10.1016/j.bmcl.2012.08.025

来源: Elsevier

【 摘 要 】

Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes investigated in efforts to overcome hERG liabilities while having orally active, potent and selective compounds with sufficient brain penetration. A chemometric comparison of similar to 2000 diverse MCHR1 and similar to 1000 diverse hERG ligands underline the structural similarities. A binding pocket analysis of a MCHR1 model and recent X-ray structures of GPCRs invoked in selectivity issues indicate a way to support future drug design. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

Free