Design and synthesis of sulfonamidophenylethylamides as novel cardiac myosin activator.

Design and synthesis of sulfonamidophenylethylamides as novel cardiac myosin activator. Bioorg Med Chem. 2019 Jul 27;: Authors: Manickam M, Pillaiyar T, Namasivayam V, Boggu PR, Sharma N, Jalani HB, Venkateswararao E, Lee YJ, Jeon ES, Son MJ, Woo SH, Jung SH Abstract The sulfonamidophenylethylamide analogues were explored for finding novel and potent cardiac myosin activators. Among them, N-(4-(N,N-dimethylsulfamoyl)phenethyl-N-methyl-5-phenylpentanamide (13, CMA at 10 µM = 48.5%; FS = 26.21%; EF = 15.28%) and its isomer, 4-(4-(N,N-dimethylsulfamoyl)phenyl-N-methyl-N-(3-phenylpropyl)butanamide (27, CMA at 10 µM = 55.0%; FS = 24.69%; EF = 14.08%) proved to be efficient cardiac myosin activators both in in vitro and in vivo studies. Compounds 13 (88.2 + 3.1% at 5 µM) and 27 (46.5 + 2.8% at 5 µM) showed positive inotropic effect in isolated rat ventricular myocytes. The potent compounds 13 and 27 were highly selective for cardiac myosin over skeletal and smooth muscle myosin, and therefore these potent and selective amide derivatives could be considered a new class of cardiac myosin activators for the treatment of systolic heart failure. PMID: 31378598 [PubMed - as supplied by publisher]
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research