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Discovery and Characterization of 2‐(Cyclopropanesulfonamido)‐ N ‐(2‐ethoxyphenyl)benzamide, ML382: a Potent and Selective Positive Allosteric Modulator of MrgX1
Author(s) -
Wen Wandong,
Wang Yan,
Li Zhe,
Tseng PangYen,
McManus Owen B.,
Wu Meng,
Li Min,
Lindsley Craig W.,
Dong Xinzhong,
Hopkins Corey R.
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402277
Subject(s) - allosteric regulation , benzamide , allosteric modulator , potency , chemistry , ligand (biochemistry) , stereochemistry , pharmacology , small molecule , structure–activity relationship , drug discovery , receptor , in vitro , biochemistry , medicine
Previous studies have shown that the activation of mouse MrgC11, a G‐protein‐coupled receptor, by its peptide ligand BAM8‐22 can inhibit chronic pain. A large‐scale screen has been carried out to isolate small‐molecule allosteric agonists of MrgX1, the human homologue of MrgC11. The goal of this study is to improve the efficacy and potency of positive allosteric modulators (PAMs) with therapeutic implications in combating chronic pain. Herein we report an iterative parallel synthesis effort and a structure–activity relationship study of a series of arylsulfonamides which led to the discovery of the first PAM of MrgX1, ML382.