Discovery of DS-3801b, a non-macrolide GPR38 agonist with N-methylanilide structure. (1st March 2022)

• Record Type: Journal Article
• Authors: Toda, Narihiro; Shida, Takeshi; Takano, Rieko; Katagiri, Takahiro; Hirouchi, Masakazu; Abe, Manabu; Soma, Kaori; Nakagami, Yasuhiro; Yamazaki, Mami
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 59(2022)
• Publication Date: 2022-03-01
• Subjects: Motilin -- Motilin receptor agonist -- GPR38 -- Constipation -- DS-3801; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.128554
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Motilin is a 22-amino-acid gastrointestinal (GI) hormone and is involved in the regulation of GI motility through binding to GPR38, the motilin receptor which is expressed on smooth muscle cells in the GI tract. Therefore, GPR38 agonists are expected to be novel gastrointestinal prokinetic agents for the treatment of functional gastrointestinal disorders such as gastroparesis and chronic constipation. We identified a series of N -methylanilide derivatives as novel non-macrolide GPR38 agonists. Among them, 12 di-l -tartrate (DS-3801b) was selected as a clinical candidate for further evaluation.