| Literature DB >> 22487182 |
Sanjita Sasmal1, Gade Balaji, Hariprasada R Kanna Reddy, D Balasubrahmanyam, Gujjary Srinivas, Shivakumar Kyasa, Pradip K Sasmal, Ish Khanna, Rashmi Talwar, J Suresh, Vikram P Jadhav, Syed Muzeeb, Dhanya Shashikumar, K Harinder Reddy, V J Sebastian, Thomas M Frimurer, Øystein Rist, Lisbeth Elster, Thomas Högberg.
Abstract
Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biological activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. Clusters of refined hMCHR1 homology models derived from the X-ray structure of the β2-adrenergic receptor, including extracellular loops, were developed and used to guide the design.Entities:
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Year: 2012 PMID： 22487182 DOI： 10.1016/j.bmcl.2012.03.050
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823