Substituted pyrido[3,2-b]oxazin-3(4H)-ones: synthesis and evaluation of antinociceptive activity.

Abstract A new series of N -substituted pyrido[3,2- b ]oxazinones has been synthesized, pharmacologically evaluated, and compared with acetyl salicylic acid. The compound with the maximal combination of safety and analgesic efficacy was 4-{3-[4-(4-fluorophenyl-1-piperazinyl)propyl]}-2 H -pyrido[3,2- b ]-1,4-oxazin-3(4 H )-one ( 6c ) with ED 50 values of 12.5 mg/kg po (mouse: phenylquinone writhing test) and 27.8 mg/kg po (rat: acetic acid writhing test), respectively. Compound 6c proved to be more active than aspirin with a safety index of 5.1.