Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: part 2

Sanjita Sasmal; D Balasubrahmanyam; Hariprasada R Kanna Reddy; Gade Balaji; Gujjary Srinivas; Srisailam Cheera; Chandrasekhar Abbineni; Pradip K Sasmal; Ish Khanna; V J Sebastian; Vikram P Jadhav; Manvendra P Singh; Rashmi Talwar; J Suresh; Dhanya Shashikumar; K Harinder Reddy; V Sihorkar; Thomas M Frimurer; Øystein Rist; Lisbeth Elster; Thomas Högberg

doi:10.1016/j.bmcl.2012.03.049

Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: part 2

Bioorg Med Chem Lett. 2012 May 1;22(9):3163-7. doi: 10.1016/j.bmcl.2012.03.049. Epub 2012 Mar 23.

Affiliation

¹ Discovery Research, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500049, India. [email protected]

PMID: 22497763
DOI: 10.1016/j.bmcl.2012.03.049

Abstract

Melanin concentrating hormone receptor 1 (MCHR1) antagonists have potential for the treatment of obesity and several CNS disorders. In the preceding article, we have described a novel series of quinazolines as MCHR1 antagonists and demonstrated in vivo proof of principle with an early lead. Herein we describe the detailed SAR and SPR studies to identify an optimized lead candidate having good efficacy in a sub-chronic DIO model with a good cardiovascular safety window.

MeSH terms

Cardiovascular Diseases / prevention & control
Drug Design*
Humans
Quinazolines / chemical synthesis*
Quinazolines / pharmacology
Receptors, Pituitary Hormone / antagonists & inhibitors*
Receptors, Somatostatin / antagonists & inhibitors
Structure-Activity Relationship

Substances

MCHR1 protein, human
Quinazolines
Receptors, Pituitary Hormone
Receptors, Somatostatin
melanin-concentrating hormone receptor