No-mimetic furoxans: arylsulphonylfuroxans and related compounds.
A new class of methylfuroxans and methylfurazans arylthio, arylsulphinyl and arylsulphonyl substituted, characterized by vasodilating and antiaggregatory properties, is described. Vasodilating activity, tested on rabbit aortic rings percontracted with 1 microM noradrenaline, is enhanced by N-oxidation of the furazan ring and is maximized by increase of the sulphur atom oxidation level. Compounds 4-methyl-3-(p-methoxyphenylsulphonyl) furoxan 6c, 3-phenyl-4-phenylsulphonylfuroxan 10, 4-phenyl-3-phenylsulphonylfuroxan 11 and 3,4-bis(phenyl-sulphonyl)furoxan 12 (EC50 values ranging between 0.055-1.07 microM), seem to be promising since they show the highest potency as well as maximal efficacy, causing complete reversal of noradrenaline induced contraction. The structure-activity relationship, observed in the platelet aggregation test, is substantially similar to that reported for the vasodilating activity, in line with the general profile of these drugs as putative NO-mimetic derivatives.
Ferioli
R
R
Centro di Studio e Ricerca di Farmacologia Cardiopolmonare Sperimentale, Istituto di Scienze Farmacologiche, Facoltà di Farmacia, Italy.
Fazzini
A
A
Folco
G C
GC
Fruttero
R
R
Calvino
R
R
Gasco
A
A
Bongrani
S
S
Civelli
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000494:pharmacology*
D010069:Oxadiazoles; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents