| Literature DB >> 30006176 |
Kenneth J Wilson1, Jingbo Xiao1, Catherine Z Chen1, Zaohua Huang2, Irina U Agoulnik2, Marc Ferrer1, Noel Southall1, Xin Hu1, Wei Zheng1, Xin Xu1, Amy Wang1, Courtney Myhr2, Elena Barnaeva1, Emmett R George1, Alexander I Agoulnik2, Juan J Marugan3.
Abstract
A dose responsive quantitative high throughput screen (qHTS) of >350,000 compounds against a human relaxin/insulin-like family peptide receptor (RXFP1) transfected HEK293 cell line identified 2-acetamido-N-phenylbenzamides 1 and 3 with modest agonist activity. An extensive structure-activity study has been undertaken to optimize the potency, efficacy, and physical properties of the series, resulting in the identification of compound 65 (ML-290), which has excellent in vivo PK properties with high levels of systemic exposure. This series, exemplified by 65, has produced first-in-class small-molecule agonists of RXFP1 and is a potent activator of anti-fibrotic genes.Entities:
Keywords: 2-Acetamido-N-Phenylbenzamide; Antifibrotic; G-protein coupled receptor; Relaxin
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Year: 2018 PMID： 30006176 PMCID： PMC6102074 DOI： 10.1016/j.ejmech.2018.06.008
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514