Synthesis and anti-inflammatory activity of some heterocyclic derivatives of phenothiazine.

摘要

Some new 10-{[5'-amino-(1"-ace tyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-thiadiazol-2'-yl] methyl}-phenothiazines (11-16) and 10-{[5'-amino-(1"-acetyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazines (26-31) have been synthesized from 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-thiadiazol-2'-yl)]methyl}phenothiazines (5-10) and 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-oxadiazol-2'-yl)]methyl}phenothiazines (20-25), respectively. All these compounds of the present series have been screened in vivo for their anti-inflammatory and acute toxicity. Compounds 16 and 31 were found to be potent members of the present series, which showed 46.2% and 48.0% anti-inflammatory activity, respectively, at a dose of 50 mg/kg p.o., while standard drug, phenylbutazone, exhibited 44.52% anti-inflammatory activity at same dose. However, 10-{[5'-amino-(1"-acetyl-5"-(o-methoxyphenyl)-2"-pyrazolin-3"-yl)-1',3',4' -oxadiazol-2'-yl]methyl}phenothiazine (31) was found to be most active and less ulcerogenic compound of this series. The structure of these compounds have been elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis.