Synthesis and SAR of 5-aryl-furan-2-carboxamide derivatives as potent urotensin-II receptor antagonists. Issue 4 (15th February 2019)

• Record Type: Journal Article
• Authors: Lim, Chae Jo; Kim, Nam Hui; Park, Hye Jin; Lee, Byung Ho; Oh, Kwang-Seok; Yi, Kyu Yang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 4(2019)
• Page Start: 577
• Page End: 580
• Publication Date: 2019-02-15
• Subjects: Urotensin-II receptor -- Antagonists -- 5-Aryl-furan-2-carboxamide -- Cardiovascular disease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.12.058
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: The synthesis and SAR of 5-arylfuran-2-carboxamide derivatives as urotensin-II receptor antagonists are described. Abstract: The synthesis and biological evaluation as potential urotensin-II receptor antagonists of a series of 5-arylfuran-2-carboxamide derivatives1, bearing a 4-(3-chloro-4-(piperidin-4-yloxy)benzyl)piperazin-1-yl group, are described. The results of a systematic SAR investigation of furan-2-carboxamides with C-5 aryl groups possessing a variety of aryl ring substituents led to identification of the 3, 4-difluorophenyl analog1y as a highly potent UT antagonist with an IC50 value of 6 nM. In addition, this substance was found to display high metabolic stability, and low hERG inhibition and cytotoxicity, and to have an acceptable PK profile.