A new class of ibuprofen derivatives with reduced gastrotoxicity.
A new series of nonsteroidal antiinflammatory drugs (NSAIDs) obtained by linking ibuprofen to selected furoxan moieties and to related furazans were synthesized and tested for their antiinflammatory, antiaggregatory, and ulcerogenic properties. All the derivatives are endowed with antiinflammatory activity comparable to that of ibuprofen, but, unlike this drug, they display reduced acute gastrotoxicity. The masking of the ibuprofen-free carboxylic group seems to be principally at the basis of this reduced topical irritant action. The two furoxan derivatives 8 and 9 also trigger potent antiaggregatory effects, principally as a consequence of their NO-donor ability.
Lolli
M L
ML
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
Cena
C
C
Medana
C
C
Lazzarato
L
L
Morini
G
G
Coruzzi
G
G
Manarini
S
S
Fruttero
R
R
Gasco
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002351:Carrageenan; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004487:Edema / Q000188:drug therapy; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010437:Peptic Ulcer / Q000139:chemically induced; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
C438592:3-(3-(benzenesulfonyl)furoxan-4-yloxy)propyl 2-(4-isobutylphenyl)propionate; C438593:3-(3-(phenylthio)furoxan-4-yloxy)propyl 2-(4-isobutylphenyl)propionate; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003497:Cyclic N-Oxides; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010975:Platelet Aggregation Inhibitors; C010166:furoxans; D002351:Carrageenan; D007052:Ibuprofen