Synthesis and Positive Inotropic Evaluation of (E)‐2‐(4‐Cinnamylpiperazin‐1‐yl)‐N‐(1‐substituted‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamides

Abstract

A series of (E)-2-(4-cinnamylpiperazin-1-yl)-N-(1-substituted-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume on isolated rabbit heart preparations. This class of compounds presented favorable in vitro activity compared with the standard drug, milrinone, among which N-(1-(3-chlorophenyl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-cinnamylpiperazin-1-yl)acetamide 5e was found to be the most potent with 16.58 ± 0.11% increased stroke volume (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5) M. The chronotropic effects of the compounds having inotropic effects were also evaluated.

Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design, Synthesis, and Bio‐Activity

“…The developed synthetic route is depicted in Scheme . Initially, we examined the preparation of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline hydrochloride ( 3 ) from the reaction of 6‐nitro‐3,4‐dihydroquinoline‐2(1H)‐thione ( 2 ) and tert ‐butyl 4‐(hydrazinecarbonyl) piperidine‐1‐carboxylate ( 1 ) by following the reported literature with some modifications in order to introduce piperidine moiety to triazole at the second position . Further, the compound 3 when reacted with various electron withdrawing and donating aryl sulfonyl chlorides and cyclopropyl sulfonyl chloride ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j ) in the presence of triethyl amine obtained the corresponding title compounds as 1‐(1‐(aryl/cyclopropylsulfonyl)piperidin‐4‐yl)‐7‐nitro‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) (Table ).…”

“…To a stirred solution of 6‐nitro‐3, 4‐dihydroquinoline‐2(1H)‐thione ( 2 ) (3.5 g, 1.6 mmol) in acetonitrile (50 mL) was added ter t‐butyl 4‐(hydrazine carbonyl)piperidine‐1‐carboxylate ( 1 ) (4.1 g, 1.6 mmol) drop wise and was stirred at reflux temperature for 6 h. After completion of reaction, the reaction mixture was cooled at room temperature and diluted with ethylacetate, washed with water, and dried over sodium sulfate. The crude product was purified by column chromatography to afford tert ‐butyl 4‐(7‐nitro‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐1‐yl)piperidine‐1‐carboxylate (3.3 g, 51%) as a white solid.…”