Reversed ester analogues of pethidine: isomeric 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidines

The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me, c-6-Me, r-4-OCOMe isomer was an effective analgesic in mice (2.3 X pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl alpha- to nitrogen and the lowering action of equatorial alpha-methyl substituents in reversed esters of pethidine.