Synthesis and biological activity of 1-phenylsulfonyl-4-phenylsulfonylaminopyrrolidine derivatives as thromboxane a(2) receptor antagonists

Bioorg Med Chem. 2002 May;10(5):1399-415. doi: 10.1016/s0968-0896(01)00397-2.

Abstract

The synthesis and biological activity of novel 1-phenylsulfonyl-4- phenylsulfonylaminopyrrolidine analogues are described. All compounds were produced through modification of the substituent formally corresponding to the 1,3-dioxane ring system and the omega-octenol side chain of thromboxane A(2) (TXA(2)), in reference to the structure of Daltroban. Several compounds were found to be potent TXA(2) receptor antagonists. Compound 51a was the most effective inhibitor of 9,11-epoxymethano PGH(2) (U-46619)-induced rat aortic strip contraction (IC(50)=0.48 nM).

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / antagonists & inhibitors
  • Animals
  • Aorta
  • Disease Models, Animal
  • Dogs
  • Guinea Pigs
  • Haplorhini
  • Humans
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Platelet Aggregation / drug effects
  • Pulmonary Embolism / drug therapy
  • Pulmonary Embolism / prevention & control
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*
  • Rabbits
  • Rats
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Thrombosis / drug therapy
  • Thrombosis / prevention & control
  • Vasoconstrictor Agents / antagonists & inhibitors

Substances

  • Pyrrolidines
  • Receptors, Thromboxane
  • Sulfonamides
  • Vasoconstrictor Agents
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid