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首页> 外文期刊>International Journal of Quantum Chemistry >A study of ring-substituent influence on pharmacological activity in a series of phenethylamine-type psychedelics
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A study of ring-substituent influence on pharmacological activity in a series of phenethylamine-type psychedelics

机译：环取代基对一系列苯乙胺型迷幻药的药理活性的影响研究

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Geometry optimization for each member of a series of 15 substituted phenethylamines with reported psychotomimetic activity was performed using MM2 and MOPAC93 (AM1) methods. This was followed by calculation of previously developed, numerically unitary structure indices, viz., the molecular transform indices FTm, FTe, and FTc, indicating general, electronic, and charge properties respectively, and the analogous normalized molecular moment indices M-n, M-e, and M-c. Each of the indices was used independently with the pharmacological data in a procedure to generate clusters containing three or more data points; linear correlations within each cluster were then determined. The M-n index performed best under the criteria, giving three clusters containing a total of 10 compounds; the other indices gave clusters accounting for totals of five to eight compounds for each index. Analysis of the clusters indicated that the 2- and 5-positions on the phenyl ring should have substituents and that substitution at the 4-position, preferably with a halogen, methyl, or thioether group, was critical for maximum pharmacological activity. The latter results suggest that ease of metabolic hydroxylation at the 4-phenyl position (or the substituent group at that position, e.g., methyl, ethyl, etc.) is necessary for maximum activity. The performance of the M-n index appears to indicate more of a dependence on 3D spatial requirements for bioactivity, with molecular electronic and charge properties, respectively, being of secondary importance. Further, clustering and correlation regression of the biological data on the calculated logarithm of the octanol/water partition coefficient (CLogP) showed that the latter may be an important factor influencing pharmacological activity in this series. (C) 2004 Wiley Periodicals, Inc.
机译：使用MM2和MOPAC93（AM1）方法对具有报道的拟精神活性的一系列15种取代苯乙胺中的每个成员进行几何优化。然后计算先前开发的数值单一结构指数，即分子转化指数FTm，FTe和FTc，分别表示一般性质，电子性质和电荷性质，以及类似的归一化分子矩指数Mn，Me和麦克每个指标与药理学数据一起独立使用，以生成包含三个或更多数据点的聚类。然后确定每个聚类内的线性相关性。在该标准下，M-n指数表现最佳，给出了三个簇，其中总共包含10种化合物。其他指数给出的簇则占每个指数总共五到八种化合物的总和。对簇的分析表明，苯环上的2-位和5-位应具有取代基，并且在4-位上的取代，优选被卤素，甲基或硫醚基取代，对于最大药理活性至关重要。后一结果表明，为了最大活性，在4-苯基位置（或在该位置的取代基，例如甲基，乙基等）的代谢羟基化的容易度是必需的。 M-n指数的表现似乎表明，生物活性对3D空间要求的依赖性更大，而分子电子和电荷特性分别具有次要的重要性。此外，对辛醇/水分配系数（CLogP）的计算对数的生物学数据的聚类和相关回归表明，后者可能是影响该系列药理活性的重要因素。 （C）2004年Wiley Periodicals，Inc.

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