1-Imidazolylcarbonyloxy-substituted tetrahydroquinolines and pyridines: synthesis and evaluation of P450 TxA2 inhibition

Arch Pharm (Weinheim). 1999 Oct;332(10):358-62. doi: 10.1002/(sici)1521-4184(199910)332:10<358::aid-ardp358>3.0.co;2-d.

Abstract

The title compounds are derived from our model describing structural requirements for strong P450 TxA2 inhibition. In the present paper the syntheses of the 1-imidazolylcarbonyloxy-substituted tetrahydroquinolines 1, 3, and 4, tetrahydro-naphthalene 2 and 3-ethylpyridines 5 and 6 are described. Using our P450 TxA2 inhibition assay, 1-6 were tested for enzyme inhibitory activity. Compound 1 (5-(1-imidazolylcarbonyloxy)-5,6,7,8-tetrahydroquinoline) turned out to be the most active derivative showing a potency similar to the reference compound dazoxiben (IC50 values 1.6 and 1.1 microM).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Thromboxane-A Synthase / antagonists & inhibitors
  • Thromboxane-A Synthase / blood

Substances

  • Pyridines
  • Quinolines
  • Thromboxane-A Synthase