Potent ACE inhibitors from 5-hydroxy indanone derivatives

Abstract

A novel triazole derivatives(±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b]furan-6(2H)-one (12a-j) were designed and synthesized by the reaction between racemic azide and terminal acetylenes under click chemistry reaction conditions followed by biological evaluation as angiotensin converting enzyme (ACE) inhibitors. β-Amino alcohol derivatives of 1-indanone (15a-l) were synthesized from 5-hydroxy indanone, it was reacted with epichlorohydrin and followed by oxirane ring opening with various piperazine derivatives. Among the newly synthesized compounds 12b (IC₅₀: 1.388024 µM), 12g (IC₅₀: 1.220696 µM), 12j (IC₅₀: 1.312428 µM) and 15k (IC₅₀: 1.349671 µM) and 15l (IC₅₀: 1.330764 µM) emerged as most active non-carboxylic acid ACE inhibitors with minimal toxicity comparable to clinical drug Lisinopril.

Keywords: ACE inhibitors; Click chemistry; Epi-chlorohydrin; Hypertension; Piperazines; Triazoles; β-Amino alcohols.