Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1

J Med Chem. 1992 Sep 4;35(18):3394-402. doi: 10.1021/jm00096a016.


A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.

MeSH terms

  • Animals
  • Cattle
  • Guinea Pigs
  • Male
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Thromboxane
  • Structure-Activity Relationship
  • Thromboxane A2 / metabolism*
  • Thromboxane-A Synthase / antagonists & inhibitors


  • Platelet Aggregation Inhibitors
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Thromboxane A2
  • Thromboxane-A Synthase