Synthesis and pharmacological characterization of a novel nitric oxide-releasing diclofenac derivative containing a benzofuroxan moiety.
1-oxy-benzo[1,2,5]oxadiazol-5-ylmethyl [2-(2,6-dichloro-phenylamino)-phenyl]-acetate, a new diclofenac derivative bearing a benzofuroxan heterocyclic moiety in its structure, was prepared by the reaction of sodium diclofenac and 5-bromomethyl-benzo[1,2,5]oxadiazole 1-oxide. Pharmacological characterization of this modified diclofenac maintained the anti-inflammatory activity similar to its parent compound assayed in vitro and in vivo. The ulcerogenic properties of native diclofenac were not observed with this modified compound, despite the inhibition of prostaglandin E2 gastric content. The better gastric tolerability seems to be related to nitric oxide release ability.
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, 12916-900 Bragança Paulista, SP, Brazil.
Paulo Sérgio
PS
de Carvalho
Marta
M
Maróstica
Alessandra
A
Gambero
José
J
Pedrazzoli
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000737:chemistry*; D002351:Carrageenan / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004008:Diclofenac / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014456:Ulcer / Q000139:chemically induced; D010069:Oxadiazoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; D002351:Carrageenan; D051546:Cyclooxygenase 2; D004008:Diclofenac; D015232:Dinoprostone; D009569:Nitric Oxide; C014354:benzofuroxan; D010069:Oxadiazoles