Literature DB >> 26235947

Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome.

Simon D P Baugh1, Praveen K Pabba2, Joseph Barbosa2, Eric Coulter3, Urvi Desai3, Jason P Gay3, Suma Gopinathan3, Qiang Han2, Rajee Hari3, S David Kimball2, Huy V Nguyen2, Chi-You Ni2, David R Powell3, Arian Smith3, Kristen M Terranova2, Alan Wilson3, Xuan-Chuan Yu3, Victoria K Lombardo2.   

Abstract

The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Delta-5 desaturase; In vivo efficacy; Indazole; Metabolic syndrome; Ring constraint

Mesh：

Substances：

Year:  2015        PMID： 26235947     DOI： 10.1016/j.bmcl.2015.07.066

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  5 in total

1.  T-3364366 Targets the Desaturase Domain of Delta-5 Desaturase with Nanomolar Potency and a Multihour Residence Time.

Authors:  Ikuo Miyahisa; Hideo Suzuki; Atsushi Mizukami; Yukiya Tanaka; Midori Ono; Mark S Hixon; Junji Matsui
Journal:  ACS Med Chem Lett       Date:  2016-08-10       Impact factor: 4.345

2.  Fatty acid desaturase 1 knockout mice are lean with improved glycemic control and decreased development of atheromatous plaque.

Authors:  David R Powell; Jason P Gay; Melinda Smith; Nathaniel Wilganowski; Angela Harris; Autumn Holland; Maricela Reyes; Laura Kirkham; Laura L Kirkpatrick; Brian Zambrowicz; Gwenn Hansen; Kenneth A Platt; Isaac van Sligtenhorst; Zhi-Ming Ding; Urvi Desai
Journal:  Diabetes Metab Syndr Obes       Date:  2016-06-22       Impact factor: 3.168

3.  A Novel Selective Inhibitor of Delta-5 Desaturase Lowers Insulin Resistance and Reduces Body Weight in Diet-Induced Obese C57BL/6J Mice.

Authors:  Hiroaki Yashiro; Shuichi Takagahara; Yumiko Okano Tamura; Ikuo Miyahisa; Junji Matsui; Hideo Suzuki; Shota Ikeda; Masanori Watanabe
Journal:  PLoS One       Date:  2016-11-10       Impact factor: 3.240

4.  Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine.

Authors:  Katherine Castor; Jessica Dawlaty; Xianghong Arakaki; Noah Gross; Yohannes W Woldeamanuel; Michael G Harrington; Robert P Cowan; Alfred N Fonteh
Journal:  Front Mol Neurosci       Date:  2021-08-31       Impact factor: 5.639

Review 5.  Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease.

Authors:  Aleksandra Czumaj; Tomasz Śledziński
Journal:  Nutrients       Date:  2020-01-29       Impact factor: 5.717
  5 in total

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