Tsai Y C, Liou J P, Liao R, Cheng C Y, Tao P L
Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
Bioorg Med Chem Lett. 1998 Jul 21;8(14):1813-8. doi: 10.1016/s0960-894x(98)00318-7.
Among a series of C-alkylated analogs of the weak mu opioid ligand spiro[benzofuran-3(2H),4'-1'-methylpiperidine-7-ol] (1), the 2-methyl, 2-ethyl, and cis 3'-methyl analogs, namely compounds (+/-)2, (+/-)-3, and (+/-)-4, showed much enhanced mu-affinities, with (+/-)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (+/-)-5 remained a weak mu-binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.
在弱μ阿片样物质配体螺苯并呋喃-3(2H),4'-1'-甲基哌啶-7-醇的一系列C-烷基化类似物中，2-甲基、2-乙基和顺式3'-甲基类似物，即化合物(±)2、(±)-3和(±)-4，显示出显著增强的μ亲和力，其中(±)-4几乎与(-)-吗啡一样有效；而反式3'-甲基类似物(±)-5仍然是一种弱μ结合剂。能量计算和核磁共振数据表明，化合物2-4有利于苯基轴向构象，而化合物1和5有利于苯基赤道构象。
