Selective thyroid hormone receptor β agonists with oxadiazolone acid isosteres. Issue 21 (1st November 2020)

• Record Type: Journal Article
• Authors: Kirschberg, Thorsten A.; Jones, Christopher T.; Xu, Yingzi; Fenaux, Martijn; Halcomb, Randall L.; Wang, Yujin; Klucher, Kevin
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 21(2020)
• Publication Date: 2020-11-01
• Subjects: Thyroid hormone receptor -- Hypercholesterolemia -- NASH; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127465
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Use of the oxadiazolone acid isostere in triiodothyronine analogs yielded potent and selective agonists for the thyroid hormone receptor β. Selected examples showed good in-vivo efficacy in a rat hypercholesterolemic model. One compound was further profiled in a diet-induced mouse model of nonalcoholic steatohepatitis (NASH) and showed robust target engagement and significant histological improvements in both liver steatosis and fibrosis.