A study of the biologically active conformers for prodine opiates and their derivatives
A study of the biologically active conformers for prodine opiates and their derivatives
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阿片类普罗定及其衍生物生物活性构象异构体的研究
DOI：
10.1002/jcc.540050602
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发表时间：
1984
影响因子：
3
通讯作者：
P. Kollman
中科院分区：
文献类型：
--
作者：
M. Froimowitz;P. Kollman
构象能量计算使用经验MM 2（分子力学II）和半经验量子力学PCILO（微扰配置相互作用使用本地化轨道）的方法报告各种脯氨酸衍生物。这些包括3-去甲基脯氨酸、α-脯氨酸、β-脯氨酸、α-2-甲基衍生物、α-普罗米多、γ-2，3-二甲基衍生物和γ-异普罗米多。结果是一致的，所有的化合物激活阿片受体的苯基赤道构象与最佳的活性，从一个特定的方向的苯基和丙氧基。与之前有限的实验数据不一致，发现α-普罗美多更倾向于苯基赤道构象。经证实，在3-去甲基脯胺优选的两种镜像苯基赤道构象中，活性更高的脯胺对映体始终优选苯基取向与吗啡中发现的苯基取向相反（镜像）的对映体和吗啡样（+）-苯基吗啡烷的优选构象。这是一个可能的分子基础的非吗啡样的影响，发生与引入苯基Meta羟基到一些脯氨酸衍生物。还表明，具有吗啡样苯基取向的活性较低的脯氨酸对映体可能以吗啡样方式作用于阿片受体。
Conformational energy calculations using the empirical MM2 (molecular mechanics II) and semiempirical quantum mechanical PCILO (perturbative configuration interaction using localized orbitals) methods are reported for various prodine derivatives. These include 3‐demethylprodine, α‐prodine, β‐prodine, the α‐2‐methyl derivative, α‐promedol, the γ‐2,3‐dimethyl derivative, and γ‐isopromedol. The results are consistent with all of the compounds activating the opiate receptor in a phenyl equatorial conformation with optimum activity resulting from a particular orientation of the phenyl and propionoxyl groups. In disagreement with previous limited experimental data, α‐promedol is found to prefer a phenyl equatorial conformer. It is confirmed that, of the two mirror image phenyl equatorial conformers that are preferred for 3‐demethylprodine, the more active prodines antipodes consistently prefer the one in which the phenyl orientation is the opposite (mirror image) of that found in morphine and in the preferred conformer of the morphine‐like (+)‐phenylmorphan. This is a possible molecular basis for the nonmorphine‐like effects that occur with the introduction of a phenyl meta hydroxyl into some prodine derivatives. It is also suggested that the less active prodine antipodes, which have a morphine‐like phenyl orientation, may act in a morphine‐like manner at opiate receptors.
丁酰胺醇和异丁酰胺醇的构象特性。
影响因子：
3.6
作者：
Froimowitz,M;Matthysse,S
通讯作者：
Matthysse,S