Synthesis and Evaluation of 2-{[(2-Oxo-1H-quinolin-8-yl)oxy]methyl}-Substituted α-Methylidene-γ-butyrolactones

✍ Scribed by Cherng-Chyi Tzeng; Yeh-Long Chen; Chyi-Jia Wang; Tai-Chi Wang; Ya-Ling Chang; Che-Ming Teng

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: German
• Weight: 509 KB
• Volume: 80
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19970800413

✦ Synopsis

Abstract

O‐Alkylation of 8‐hydroxy‐1__H__‐quinolin‐2‐one (1) afforded 8‐(2‐oxopropoxy)‐1__H__‐quinolin‐2‐one (2) which was immediately cyclized to form the tricyclic 2,3‐dihydro‐3‐hydroxy‐3‐methyl‐5__H__‐pyrido[1,2,3‐de][1,4]benzoxazine,‐5‐one (3). The Reformatsky‐type condensation of 3 furnished antiplatelet 8‐[(2,3,4,5‐tetrahydro‐2‐methyl‐4‐methylidene‐5‐oxofuran‐2‐yl)melhoxy]‐1__H__‐quinolin‐2‐one (4). Its counterparts 7a–f, Ph‐substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky‐type condensation. Although compound 4 was less active against platelet aggregation than 7a–f, it was the only compound which exhibited significant inhibitory activity on high‐K^+^ medium, Ca^2+^‐induced vasoconstriction and was more active than most of its Ph‐substituted counterparts against norepinephrine‐induced vasoconstrictions.