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Papers: 14 May 2022 - 20 May 2022

2022 May 12

ACS Med Chem Lett



Synthesis and Biological Characterization of a Series of 2-Sulfonamidebenzamides as Allosteric Modulators of MrgX1.


Sharma S, Peng Q, Vadukoot AK, Aretz CD, Jensen AA, Wallick AI, Dong X, Hopkins CR
ACS Med Chem Lett. 2022 May 12; 13(5):841-847.
PMID: 35586421.


The present study describes our continued efforts in the discovery and characterization of a series of 2-sulfonamidebenzamides as allosteric modulators of MrgX1. MrgX1 has been shown to be an attractive target as a nonopioid receptor for the potential treatment of chronic pain. Working from our original compound, ML382, and utilizing iterative medicinal chemistry, we have identified key halogen substituents that improve MrgX1 potency by ∼8-fold. In addition, we have evaluated the compounds in Tier 1 drug metabolism and pharmacokinetics assays and have identified key compounds that impart improved potency and microsomal stability.