Synthesis and evaluation of analgesic, anti-inflammatory and antioxidant activities of new 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones

A new series of 6-acyl-3-alkyl-5-methyl2(3H)-benzoxazolones have been obtained starting from 5-methyl-2(3H)-benzoxazolone. All the compounds have been characterized by IR, H-1-NMR and mass spectroscopy. The new compounds were screened for analgesic and anti-inflammatory activities and ulcerogenic effect. The in vitro antioxidant capacity of the synthesized compounds were tested by the nitric oxide radical scavenging assay. Most of the compounds showed anti-inflammatory activity. Among them, 3-[4-(4-fluorophenyl)piperazinomethyl]- 6-(3-chlorobenzoyl)-5-methyl-2(3H)-benoxazolone (3j) was found more potent than the reference drug indometacin (CAS 53-86-1) with 41.66% decrease in edema. Compared with the control, some of the compounds exhibited analgesic effects. Similar to the anti-inflammatory activity results, compound 3j showed the highest analgesic profile with 48.56 % inhibition. No active hemorragic focus was observed in the microscopic evaluation in the ulcerogenic effect studies of the tested compounds. 6-(3-Chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (2b) and 3-[4-(4-fluorophenyi-piperazino)methyl]-6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) showed nearly maximum antioxidant activity compared to ascorbic acid (CAS 50-81-7) with IC50 values of 27.6 and 30.1 mu g/mL, respectively.