Indenopyrazole oxime ethers: Synthesis and β1-adrenergic blocking activity

Abstract This paper reports the synthesis and cardiac activity of new β-blockers derived from (Z/E)- indeno[1,2- c ]pyrazol-4(1 H )-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-1 H- indeno[1,2 -c ]pyrazol-4-one O -((2-hydroxy-3-(substituted amino)propyl)oxime ( 7a–c ) and (Z/E)- 1-methyl-1 H- 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 β 1 -adrenergic receptors.