Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists

Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists

TGR5 is a bile acid G protein-coupled receptor (GPCR), which is an attractive therapeutic target for the treatment of obesity, and its highly associated Type 2 diabetes. Activation of TGR5 promotes secretion of glucagon like peptide-1 (GLP-1) and activates insulin secretion. Series of novel 2-mercap...

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Main Authors: Sameer Agarwal, Santosh Sasane, Jeevan Kumar, Brijesh Darji, Hitesh Bhayani, Shubhangi Soman, Neelima Kulkarni, Mukul Jain
Format: Article
Language:English
Published: Elsevier 2019-03-01
Series:Medicine in Drug Discovery
Online Access:http://www.sciencedirect.com/science/article/pii/S2590098619300028
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spelling doaj-e49487f762a94e9c8a394fa0a714e79b2020-11-25T02:19:32ZengElsevierMedicine in Drug Discovery2590-09862019-03-011Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonistsSameer Agarwal0Santosh Sasane1Jeevan Kumar2Brijesh Darji3Hitesh Bhayani4Shubhangi Soman5Neelima Kulkarni6Mukul Jain7Zydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India; Corresponding author.Zydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India; Chemistry Dept., The M.S University, Baroda 390 002, IndiaZydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, India; Chemistry Dept., The M.S University, Baroda 390 002, IndiaZydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, IndiaZydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, IndiaChemistry Dept., The M.S University, Baroda 390 002, IndiaChemistry Dept., The M.S University, Baroda 390 002, IndiaZydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad 382 210, IndiaTGR5 is a bile acid G protein-coupled receptor (GPCR), which is an attractive therapeutic target for the treatment of obesity, and its highly associated Type 2 diabetes. Activation of TGR5 promotes secretion of glucagon like peptide-1 (GLP-1) and activates insulin secretion. Series of novel 2-mercapto imidazole and triazole derivatives were designed, synthesized and evaluated for their activities as TGR5 agonists. Our medicinal chemistry efforts led to the identification of many potent compounds. In particular, triazole derivative 4m was able to stimulate hTGR5 receptors with an EC50 of 25 nM, and possess good physico-chemical profile. Keywords: TGR5, TGR5 agonist, Obesity, Type-2-diabetes, Imidazole derivatives, Triazole derivativeshttp://www.sciencedirect.com/science/article/pii/S2590098619300028
collection DOAJ
language English
format Article
sources DOAJ
author Sameer Agarwal
Santosh Sasane
Jeevan Kumar
Brijesh Darji
Hitesh Bhayani
Shubhangi Soman
Neelima Kulkarni
Mukul Jain
spellingShingle Sameer Agarwal
Santosh Sasane
Jeevan Kumar
Brijesh Darji
Hitesh Bhayani
Shubhangi Soman
Neelima Kulkarni
Mukul Jain
Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
Medicine in Drug Discovery
author_facet Sameer Agarwal
Santosh Sasane
Jeevan Kumar
Brijesh Darji
Hitesh Bhayani
Shubhangi Soman
Neelima Kulkarni
Mukul Jain
author_sort Sameer Agarwal
title Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
title_short Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
title_full Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
title_fullStr Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
title_full_unstemmed Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists
title_sort novel 2-mercapto imidazole and triazole derivatives as potent tgr5 receptor agonists
publisher Elsevier
series Medicine in Drug Discovery
issn 2590-0986
publishDate 2019-03-01
description TGR5 is a bile acid G protein-coupled receptor (GPCR), which is an attractive therapeutic target for the treatment of obesity, and its highly associated Type 2 diabetes. Activation of TGR5 promotes secretion of glucagon like peptide-1 (GLP-1) and activates insulin secretion. Series of novel 2-mercapto imidazole and triazole derivatives were designed, synthesized and evaluated for their activities as TGR5 agonists. Our medicinal chemistry efforts led to the identification of many potent compounds. In particular, triazole derivative 4m was able to stimulate hTGR5 receptors with an EC50 of 25 nM, and possess good physico-chemical profile. Keywords: TGR5, TGR5 agonist, Obesity, Type-2-diabetes, Imidazole derivatives, Triazole derivatives
url http://www.sciencedirect.com/science/article/pii/S2590098619300028
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