A Novel Series of Thromboxane A_2 Synthetase Inhibitors with Free Radical Scavenging and Anti-peroxidative Activities

Abstract

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A_2(TXA_2)synthetase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3-{5-substituted-3-[2-(imidazol-1-yl)ethyl[indolin-1-yl}propionic acids showed free radical scavenging activity and inhibitory effects on lipid-peroxidation of rat brain homogenate and on arachidonate-induced TXA_2-dependent aggregation of rabbit platelets. The anti-platelet and anti-peroxidative activities were related to the lipophilicity of the 5-substituent. The 5-hexyloxy derivative(13)showed about 35-fold higher inhibitory activity on TXA_2 synthesis than that of ozagrel and about 100-fold higher activity on lipid peroxidation than that of α-tocopherol. Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo anti-peroxidative activity in rats.

Journal

Chemical & pharmaceutical bulletin   [List of Volumes]

Chemical & pharmaceutical bulletin 49(5), 563-571, 2001-05-01  [Table of Contents]

The Pharmaceutical Society of Japan

References:  22

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Codes

  • NII Article ID (NAID) :
    110003615942
  • NII NACSIS-CAT ID (NCID) :
    AA00602100
  • Text Lang :
    ENG
  • Article Type :
    ART
  • ISSN :
    00092363
  • NDL Article ID :
    5763383
  • NDL Source Classification :
    ZS51(科学技術--薬学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No. :
    Z53-D167
  • Databases :
    CJP  NDL  NII-ELS  J-STAGE 

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