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α‐Methylidene‐γ‐butyrolactones: Synthesis and evaluation of quinolin‐2(1 H )‐one derivatives
Author(s) -
Wang TaiChi,
Chen YehLong,
Tzeng CherngChyi,
Liou ShorongShii,
Tzeng WengFeng,
Chang YaLing,
Teng CheMing
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19980810517
Subject(s) - chemistry , vasoconstriction , arachidonic acid , inhibitory postsynaptic potential , stereochemistry , tonic (physiology) , alkylation , platelet , thrombin , medicinal chemistry , biochemistry , catalysis , medicine , enzyme
As a continuation of our previous studies on the synthesis and antiplatelet activity of quinolin‐2(1 H )‐ones with an α‐methylidene‐γ‐butyrolactone substituted at O(8), the O(6)‐ and N(1)‐substituted isomers were synthesized and evaluated for antiplatelet activity against thrombin (Thr)‐, arachidonic acid (AA)‐, collagen (Col)‐, and platelet‐activating‐factor (PAF)‐induced aggregation in washed rabbit platelets. These compounds were synthesized from 6‐hydroxyquinolin‐2(1 H )‐one via alkylation and Reformatsky ‐type condensation ( Schemes 1 and 2 ). All of them were found to inhibit the platelet aggregation perfectly which was induced by AA and Col. 6‐Substituted isomers 5b – g exhibited very strong inhibitory activities against AA‐ and PAF‐ induced aggregation and are approximately ten times more potent than their 8‐substituted counterparts. However, the 1‐substituted ( 11a and 11b ) and the 1,6‐disubstituted ( 6 ) counterparts were relatively inactive. Their effects on the Ca 2+ ‐dependent vasoconstriction induced by high K + , and the phasic and tonic vasoconstrictions induced by norepinephrine (NE) in rat aorta were also evaluated. Except 5g , all of them were found to have significant inhibitory activity on the NE‐induced phasic and tonic vasoconstrictions. Compounds 6 and 11b also exhibited strong inhibitory activity on high−K + medium, Ca 2+ ‐induced vasoconstriction.