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QSAR and Action Mechanism Studies of 1-Phenylcyclohexylamine-like Drugs

Author: ZhangShaoFei
Tutor: FanYingFang
School: Shanxi University
Course: Inorganic Chemistry
Keywords: Hallucinogens Benzene ring hexylamine PCA QSAR DFT
CLC: R96
Type: Master's thesis
Year: 2010
Downloads: 44
Quote: 1
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Abstract

Benzene hexylamine (PCA) class of drugs is a special kind of low toxicity, efficient, anticonvulsant intended psychotropic drugs, research pharmacodynamic relationships and mechanism of action of the classification of the class of drug design and development and activity prediction has a very important significance. In this paper, the statistical analysis of each descriptor to establish PCA drugs QSAR model to find the active site of these drugs affect the activity of the main factors, suggesting that the mechanism of action of these drugs and receptor. The main work and conclusions: 1. DFT/B3LYP methods, structural optimization and frequency analysis of seven isomers of the PCA molecules may exist in the 6-31G basis set level; then in the 6-311 G (d , p) basis set level to do a single-point energy calculations to determine the PCA advantage of conformation based on the results. 2 on the basis of the PCA dominant conformation the eight kinds PCA optical isomer optimized structure, frequency analysis and a single point can be calculated. The results show that the physicochemical properties of each pair of isomers (EHOMO, EHOMO-1, ELUMO, ELUMO 1, μ, H) are identical. Ground state molecular orbital and the natural bond orbital analysis showed that the interaction between these isomers donor track and receptor track is very similar, electron transfer occurs mainly on the phenyl. Phenyl either as the electron donor to the receptor provide electronic, but also as an electron acceptor to accept part of the electron transfer from the amino group or a cyclohexyl group. In order to analyze the PCA optical isomers of drug activity, respectively TI, TD50 and ED50 for the dependent variable molecular descriptors for multiple linear regression analysis, and to establish the following three QSAR model: QSAR model NR s F Rcv2 (1) TI = 98.346 254.316 Q680.9040.41226.9430.6814 (2) TDso = 1041.115 308.12 Q1 2460.541Ed80.9568.68526.2320.7147 (3) ED5o = 7617.553 194.282 101.527 Q1 ELUMO80.9682.11737.6410.7672 above results show that: Q6 is the impact of the PCA The optical isomer TI activity of principal factors; cyclohexyl meta position (No. 1 carbon atom is located) for the pharmaceutically active sites of action. The Ed and ELUMO charge transfer drugs and receptor binding. 4. Calculate the the 36 PCA analogues descriptor, and to establish the appropriate QSAR model: TI = 5.08 3.599Q1 = 5.981 Q2-5.834Q4-1.808Q12 3.135 Qc-0.305Es O.192Eb-35.152ELUMO 1-0.409HN = 33, R = 0.931, s = 0.350, F = 16.552, RCV2 = 0.7466 The above results show that: the net charge, the vibrational energy, molecular orbital energy and hydrophobicity, etc. are the main factors affecting the activity of such drugs. QSAR model built above, we propose a new drug receptor mechanism model - \According to the comprehensive analysis of the model and QSAR model and mechanism, the PCA drugs classified as the electrostatic interaction type drugs. 6. A drug molecule design new methods - electronic push-pull method, and use this method to design drug molecules with high predicted activity.

QSAR and Action Mechanism Studies of 1-Phenylcyclohexylamine-like Drugs

Abstract

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