Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders

Chem Pharm Bull (Tokyo). 1991 Oct;39(10):2564-73. doi: 10.1248/cpb.39.2564.

Abstract

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.

MeSH terms

  • Animals
  • Benzothiepins / chemical synthesis*
  • Benzothiepins / pharmacology
  • Benzothiepins / therapeutic use
  • Benzoxepins / chemical synthesis*
  • Benzoxepins / pharmacology
  • Benzoxepins / therapeutic use
  • Brain Edema / drug therapy
  • Brain Ischemia / drug therapy
  • Cerebrovascular Disorders / drug therapy*
  • Flunarizine / pharmacology
  • Flunarizine / therapeutic use
  • Hypoxia, Brain / drug therapy
  • Mice
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Rats
  • Structure-Activity Relationship

Substances

  • Benzothiepins
  • Benzoxepins
  • Piperazines
  • Flunarizine