Antiplatelet α‐Methylidene‐γ‐butyrolactones: Synthesis and evaluation of quinoline, flavone, and xanthone derivatives

Abstract

Abstract As a continuation of our previous studies on the synthesis and antiplatelet activity of coumarin derivatives of α‐methylidene‐γ‐butyrolactones, certain quinoline, flavone, and xanthone derivatives 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 quinolin‐8‐ol, flavon‐7‐ol, and xanthon‐3‐ol, respectively, via alkylation and Reformatsky ‐type condensation ( Schemes 1–3 ). By the comparison with comparison with coumarin α‐methylidene‐γ‐butyrolactone 3a , flavone and xanthone derivatives, 3b and 3c , respectively, are more selective in which only AA‐ and collagen‐induced aggregation are strongly inhibited. Most of the quinoline derivatives ( 9a–e ) exhibited broad‐spectrum antiplatelet activities.