Synthesis and biological activity of novel carbacyclins having bicyclic substituents on the omega-chain

J Med Chem. 1989 Aug;32(8):1988-96. doi: 10.1021/jm00128a049.

Abstract

A number of carbacyclins having bicyclic substituents on the omega-chain have been synthesized and tested for antiplatelet aggregation activity in vitro (against collagen-induced aggregation of rat platelet), for reduction of systemic blood pressure in vivo (ability to reduce the blood pressure in anesthetized rat by iv injection), and for cytoprotective activity (protection against ethanol-induced rat gastric lesion). The most effective compound for each activity was [3aS-[2E,3a alpha,4 alpha (3R),5 beta,6a alpha]]-5-[hexahydro-5- hydroxy-4-[3-hydroxy-3-(2-indanyl)-1-propynyl]-2(1H)-pentalenylidene+ ++] pentanoic acid (compound 11a), while some 1,4-benzodioxan analogues had selectivity for organ-protective activity, and indan analogues showed selectivity in their antiaggregation activity.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis
  • Antihypertensive Agents / chemical synthesis
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged-Ring Compounds / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Epoprostenol / analogs & derivatives
  • Epoprostenol / chemical synthesis*
  • Epoprostenol / pharmacology
  • In Vitro Techniques
  • Male
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Prostaglandins, Synthetic / chemical synthesis*
  • Prostaglandins, Synthetic / pharmacology
  • Rats
  • Rats, Inbred Strains

Substances

  • Anti-Ulcer Agents
  • Antihypertensive Agents
  • Bridged Bicyclo Compounds
  • Bridged-Ring Compounds
  • Platelet Aggregation Inhibitors
  • Prostaglandins, Synthetic
  • carboprostacyclin
  • Epoprostenol