Indenopyrazole oxime ethers: Synthesis and β1-adrenergic blocking activity

This paper reports the synthesis and cardiac activity of new beta-blockers derived from (Z/E)-indeno[1,2-c] pyrazol-4(1H)-one oximes (5a,b). The latter compounds were allowed to react with epichlorohydrin, followed by reacting the oxiranyl derivatives formed (6a,b) with some aliphatic amines to give the target compounds (Z/E)-1-phenyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino)propyl) mime (7a-c) and (Z/E)-1-methyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino) propyl)oxime (8a-c). These final products 7a-c and 8a-c were evaluated for their ability to modulate the cardiac performance of a prototype mammalian heart. The results showed that, out of these molecules tested, 7b elicits a more potent depressant effect on contractility and relaxation, and competitively antagonizes beta(1)-adrenergic receptors. (C) 2015 Elsevier Masson SAS. All rights reserved.