Synthesis and anti-inflammatory properties of benzoyl, halogenobenzoyl or cinnamoyl substituted 1-benzoxepanes and 2-methyl-1-benzoxolanes

Arzneimittelforschung. 1993 Jan;43(1):44-50.

Abstract

A series of new 7-acyl substituted 1-benzoxepanes and 5-acyl substituted 2-methyl-1-benzoxolanes were synthesized and studied for anti-inflammatory properties. The benzoyl derivatives were more active than the corresponding halogenobenzoyl derivatives and previously reported structural analogues containing less methylene groups in their heterocyclic ring. The introduction of a methyl group at the 2-position of 5-cinnamoyl-1-benzoxolane heterocyclic ring significantly potentiated the activity. Anti-inflammatory and analgesic effects of 7-benzoyl-1-benzoxepane and 5-cinnamoyl-2-methyl-I-benzoxolane were less pronounced than those of indomethacin and diclofenac but greater than those of acetylsalicylic acid (ASA). Both compounds were less toxic and 5-cinnamoyl-2-methyl-1-benzoxolane was also less gastrotoxic than all the reference drugs mentioned above. Therapeutic indices of 5-cinnamoyl-2-methyl-1-benzoxolane were greater than those of diclofenac and significantly greater than those of ASA and indomethacin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Arthritis, Experimental / prevention & control
  • Bentonite
  • Benzofurans / chemical synthesis*
  • Benzofurans / pharmacology
  • Benzofurans / toxicity
  • Benzoxepins / chemical synthesis*
  • Benzoxepins / pharmacology
  • Benzoxepins / toxicity
  • Carrageenan
  • Chemical Phenomena
  • Chemistry, Physical
  • Edema / chemically induced
  • Edema / prevention & control
  • Gastric Mucosa / drug effects
  • Granuloma / chemically induced
  • Granuloma / prevention & control
  • Lethal Dose 50
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Necrosis / chemically induced
  • Necrosis / prevention & control
  • Peritonitis / chemically induced
  • Peritonitis / prevention & control
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzofurans
  • Benzoxepins
  • Bentonite
  • Carrageenan