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, Volume 11, Issue 3, pp 274–280 | Cite as

3-(1-imidazolylmethyl) indoles: potent and selective inhibitors of human blood platelet thromboxane synthetase

  • Peter E. Cross
  • Roger P. Dickinson
  • Michael J. Parry
  • Michael J. Randall
Platelets and Thrombosis

Abstract

Several 3-(1-imidazolylmethyl) indoles were tested for inhibition of the microsomal enzymes which catalyse the biosynthesis of thromboxane A2, prostaglandin I2, and prostaglandin endoperoxides. These products were measured by bioassay to assess levels of enzyme activity. The highest activity against human blood platelet thromboxane A2-synthetase was obtained with 2-cyclopropyl-3(1-imidazolylmethyl) indole (IC50 1×10−10M). This compound also exhibited the highest activity against pig aorta prostaglandin I2-synthetase (IC50 8.4×10−7M). Of much more potential therapeutic interest, 2-isopropyl-3-(1-imidazolylmethyl) indole and 3-(1-imidazolylmethyl) indole showed almost complete selectivity against thromboxane A2-synthetase. Both compounds exhibited IC50's of 2×10−8M against the latter enzyme but showed only weak effects (IC50's>10−4M) against prostaglandin I2-synthetase and ram seminal vesicle PGH2-synthetase.

Keywords

Enzyme Activity High Activity Prostaglandin Indole Selective Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1981

Authors and Affiliations

  • Peter E. Cross
    • 1
  • Roger P. Dickinson
    • 1
  • Michael J. Parry
    • 1
  • Michael J. Randall
    • 1
  1. 1.Pfizer Central ResearchPfizer LimitedSandwichUK

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