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Modeling Olanzapine Solution Growth Morphologies

机译：涂抹奥氮平溶液生长形态

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摘要

The ability to predict crystal growth habits is an important component of drug design, enabling a targeted sweep of optimal growth conditions that confer desirable properties. This article presents an investigation into the shape of olanzapine crystals grown from various solvents, exemplifying how mechanistic models of spiral growth can be applied to small molecule therapeutics. Olanzapine is recognized as the most effective treatment for schizophrenia, but a mechanistic treatment of the underlying crystal growth has yet to be established. We model spiral growth of olanzapine form I from five solvents (acetone, ethyl acetate, toluene, methyl isobutyl ketone, and n -butyl acetate), considering a dimeric growth unit and periodic bond chains consisting of interdimer bonds. The centrosymmetric dimers are stabilized by multiple C–H···π contacts. The {1 0 0} face family dominates the predicted crystal habits, in agreement with our experiments; this morphology stems from the in-plane hydrogen bonds that are exposed on the {1 0 0} surface. The close agreement between predicted morphologies and experimental determinations lends support to the hypothesis that olanzapine grows as a dimer from these solvents. This mechanistic treatment can be readily applied to other compounds.
机译：预测晶体生长习惯的能力是药物设计的重要组成部分，使得能够赋予赋予理想性能的最佳生长条件的靶向扫描。本文介绍了从各种溶剂生长的奥氮翼晶体形状的调查，示出了螺旋生长的机械模型如何应用于小分子治疗剂。奥拉扎滨被认为是精神分裂症最有效的治疗方法，但尚未建立潜在的晶体增长的机械处理。我们从五种溶剂（丙酮，乙酸乙酯，甲苯，乙酰基乙酸甲基酮和醋酸丁酯）模拟奥氮平形式I的螺旋生长，考虑二聚体生长单元和由interdimer键组成的周期性粘合链。通过多个C-H···π触点稳定酰亚数二聚体。 {1 0 0}面部家庭统治着预测的晶体习惯，同意我们的实验;该形态学源于暴露在{1 0 0}表面上的面内氢键。预测形态和实验测定之间的密切达成符合对奥氮藻作为来自这些溶剂的二聚体的假设的支持。该机械处理可以容易地应用于其他化合物。

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  • 来源
    《Crystal growth & design》 |2018年第2期|共7页
  • 作者

    Yuanyuan Sun; Carl J. Tilbury; Susan M. Reutzel-Edens; Rajni M. Bhardwaj; Jinjin Li; Michael F. Doherty;

  • 作者单位

    National Key Laboratory of Science and Technology on Micro/Nano Fabrication Department of Micro/Nano Electronics Shanghai Jiao Tong University Shanghai 200240 China;

    Department of Chemical Engineering University of California Santa Barbara California 93106 United States;

    Small Molecule Design &

    Development Eli Lilly and Company Indianapolis Indiana 46285 United States;

    Small Molecule Design &

    Development Eli Lilly and Company Indianapolis Indiana 46285 United States;

    National Key Laboratory of Science and Technology on Micro/Nano Fabrication Department of Micro/Nano Electronics Shanghai Jiao Tong University Shanghai 200240 China;

    Department of Chemical Engineering University of California Santa Barbara California 93106 United States;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 晶体学;
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