Racemic and optically active trans 2,6-dimethyl analogues of the reversed ester of pethidine.
The preparation and stereochemical characterization of (+/-)-1,trans 2,6-trimethyl-4-phenyl-4-propionoxypiperidine hydrochloride and its (+)- and (-)-antipodes are described. The absolute configurations of the antipodes were established by X-ray analysis of the corresponding (-)-4-piperidinol hydrobromide. In antinociceptive tests on mice and rats, the (+)-2S,6S ester proved the more potent antipode by factors of at least 10 (rats) and 20 (mice), a result consistent with earlier proposals made about the probable uptake conformation of pethidine reversed esters at opioid receptors.
D000700:Analgesics; D000818:Animals; D008614:Meperidine / Q000031:analogs & derivatives*; D051379:Mice; D010146:Pain / Q000188:drug therapy; D011396:Promedol / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
C050130:1,2,6-trimethyl-4-phenyl-4-propionoxypiperidine; D000700:Analgesics; D011396:Promedol; D008614:Meperidine