Indenopyrazole oxime ethers: Synthesis and β1-adrenergic blocking activity

•A new heterocyclic system indeno[1,2-c]pyrazole oxime ethers was reported.•Some derivatives of this heterocyclic system have been prepared.•A selected derivative was screened for its β1-adrenergic blocking activity.•The oxime ether (7b) reduces cardiac contractility and selectively antagonizes β1-AR.

This paper reports the synthesis and cardiac activity of new β-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)oxime (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 β1-adrenergic receptors.

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