Synthesis and antinociceptive activity of 7-aryloxysulfonyl piperidines

Compounds having structural relationships with meperidine (14) were synthesised and examined for antinociceptive activity (rat writhing test). The compounds comprised a group of 7-aryloxysulfonyl-2,7-diazabicyclo[4.1.0]hept-4-enes (8), 1,2,5,6-tetrahydropyridylidene- (9) and piperidylidene-2-aryloxysulfonamides (10) bearing N-substituents (R1 = H,Me,8-10), 3-substituents (R2 = Me, n-Bu, Ph, 8) and 6-substituents (R2 = H, Me, n-Bu, Ph, 9-10). The relative order of potency in the test was generally 10 greater than 9 greater than 8. Replacement of the R2 hydrogen substituent of 8-10d-g by a Me, n-Bu or Ph substituent generally enhanced activity. 1-Methyl-6-phenylpiperidylidene-2-phenoxysulfonamide (10g) was the most active antinociceptive agent in the series, providing 79.6% inhibition of writhing after a 50 mg kg sc dose.