Synthesis and positive inotropic evaluation of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)ac e tamides bearing piperazine and 1,4-diazepane moieties

Two series of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)ac e tamides bearing piperazine and 1,4-diazepane moieties were synthesized and screened for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Most of the deriv...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2012-07, Vol.22 (13), p.4229-4232
Main Authors: Wu, Yan, Ma, Long-Xu, Niu, Tian-Wei, Cui, Xun, Piao, Hu-Ri
Format: Article
Language:English
Subjects:
Atrium
Drugs
Heart
piperazine
Stroke
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Summary:Two series of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)ac e tamides bearing piperazine and 1,4-diazepane moieties were synthesized and screened for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Most of the derivatives exhibited better in vitro positive inotropic activity than the existing drug, milrinone, among which 2-(4-(4-chlorobenzyl)-1,4-diazepan-1-yl)-N-(1-oxo-1,2,4,5-tetrahyd r o-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6c proved to be the most potent with 15.48-0.27% increased stroke volume (milrinone: 2.46-0.07%) at a concentration of 3 A 10a5 M. The chronotropic effects of the compounds that exhibited inotropic effects were also evaluated.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2012.05.049