Casy A F, Coates J E, Rostron C
J Pharm Pharmacol. 1976 Feb;28(2):106-10. doi: 10.1111/j.2042-7158.1976.tb04107.x.
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.
本文描述了4-乙酰氧基-1,2,6-三甲基-4-苯基哌啶的三种异构形式的制备及其立体化学表征。其中，通过热板试验判断，仅反式-2-甲基、顺式-6-甲基、反式-4-乙酰氧基异构体在小鼠中是一种有效的镇痛药（为哌替啶的2.3倍）。这些结果与已报道的数据一起，证明了在哌替啶的反向酯中，氮原子α位的轴向甲基具有增强药效的作用，而赤道面α-甲基取代基具有降低药效的作用。
