The anti-inflammatory activity of 5H-dibenz[c,e]azepine-5,7(6H)dione, 6,7-dihydro-5H-dibenz[c,e]azepine, N-benzoylbenzamide and 1H-benz[d,e]isoquinoline-1,3(2H)dione derivatives in rodents.
A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N-benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N-butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline-1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Simlot
R
R
Oswald
C B
CB
Murthy
A R
AR
elSourady
H
H
Chapman
J M
JM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002417:Cattle; D003984:Dibenzazepines / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D003984:Dibenzazepines; D007546:Isoquinolines