Synthesis and anti-inflammatory properties of benzoyl, halogenobenzoyl or cinnamoyl substituted 1-benzoxepanes and 2-methyl-1-benzoxolanes.
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.
Dauksas
V
V
Faculty of Chemistry, Vilnius University, Lithuania.
Gaidelis
P
P
Petrauskas
O
O
Udrenaite
E
E
Gasperaviciene
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001169:Arthritis, Experimental / Q000517:prevention & control; D001546:Bentonite; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001584:Benzoxepins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002351:Carrageenan; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005753:Gastric Mucosa / Q000187:drug effects; D006099:Granuloma / Q000139:chemically induced / Q000517:prevention & control; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D010538:Peritonitis / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D001584:Benzoxepins; D001546:Bentonite; D002351:Carrageenan