New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors

Bioorg Med Chem Lett. 1998 Jun 2;8(11):1381-6. doi: 10.1016/s0960-894x(98)00221-2.

Abstract

A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregation of human platelets with an IC50 value of 0.063 microM and shows a long duration of action in different species after oral administration.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / antagonists & inhibitors
  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / pharmacology
  • Pressure
  • Rabbits
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / pharmacology
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / pharmacology
  • Thromboxane-A Synthase / antagonists & inhibitors*
  • Thromboxane-A Synthase / blood
  • Trachea / drug effects
  • Trachea / physiology

Substances

  • 2-(4-chlorophenylsulfonamido)-6-propyl-7-((pyridin-3-yl)methyl)-1,2,3,4-tetrahydronaphthalene-5-propanoic acid
  • Enzyme Inhibitors
  • Platelet Aggregation Inhibitors
  • Receptors, Thromboxane
  • Sulfonamides
  • Tetrahydronaphthalenes
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Thromboxane-A Synthase