[5-(diethylamino)-2-methylpent-3-yn-2-yl] (2S)-2-cyclohexyl-2-hydroxy-2-phenylacetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [5-(diethylamino)-2-methylpent-3-yn-2-yl] (2S)-2-cyclohexyl-2-hydroxy-2-phenylacetate
• 化学式: C₂₄H₃₅NO₃
• 分子量: 385.5
• InChiKey: DMEPDNFRHUGNPT-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

Ac1mip3e 已知的人类代谢物包括 N-去乙基化的 ac1mip3e 和 4-顺式-OH ac1mip3e。

Ac1mip3e has known human metabolites that include N-deethylated ac1mip3e and 4-cis-OH ac1mip3e.

来源:NORMAN Suspect List Exchange

文献信息

• METHOD FOR PREDICTING ACTIVATION ENERGY USING AN ATOMIC FINGERPRINT DESCRIPTOR OR AN ATOMIC DESCRIPTOR
  申请人：Bioinformatics&Molecular Design Research Center

  公开号：EP2354987A2

  公开（公告）日：2011-08-10

  The present invention provides a method for constructing a database of atomic fingerprint descriptors. The invention provides a method for predicting activation energy using an atomic fingerprint descriptor and an atomic descriptor, the method comprising the steps of: (i) calculating the atomic fingerprint descriptor of a substrate; (ii) comparing the calculated atomic fingerprint descriptor with the constructed atomic fingerprint descriptor database to select an atomic position where cytochrome P450-mediated metabolism occurs; and (iii) predicting activation energy for the selected atomic position using an atomic descriptor. Also, the invention provides a method of predicting the activation energy of CYP450-mediated phase I metabolism using effective atomic descriptors. Specifically, the invention provides a method of predicting the activation energy either for cytochrome P450-mediated hydrogen abstraction or for tetrahedral intermediate formation in cytochrome P450-aromatic hydroxylation using equations including effective atomic descriptors. The method of the invention can rapidly predict activation energy for phase I metabolites at a practical level without having to perform a docking experiment between any additional CYP450 and the substrate, or a quantum mechanical calculation, thereby making it easier to develop new drugs using a computer. Also, the present invention may propose a strategy for increasing the bioavailability of drugs through the avoidance of metabolites based on the possibility of drug metabolism. Furthermore, the method of the present invention proposes new empirical approaches which can also be easily applied to activation energies for various chemical reactions, and makes it possible to explain physical and chemical factors that determine activation energy. In addition, through the prediction of activation energy according to the present invention, it is possible to predict i) metabolic products, ii) the relative rate of metabolism, iii) metabolic regioselectivity, iv) metabolic inhibition, v) drug-drug interactions, and vi) the toxicity of a metabolite.

  本发明提供了一种构建原子指纹描述符数据库的方法。本发明提供了一种使用原子指纹描述符和原子描述符预测活化能的方法，该方法包括以下步骤：(i) 计算底物的原子指纹描述符；(ii) 将计算的原子指纹描述符与构建的原子指纹描述符数据库进行比较，以选择细胞色素 P450 介导的代谢发生的原子位置；以及 (iii) 使用原子描述符预测所选原子位置的活化能。此外，本发明还提供了一种利用有效原子描述符预测 CYP450 介导的 I 期代谢活化能的方法。具体来说，本发明提供了一种利用包括有效原子描述符的方程预测细胞色素 P450 介导的氢抽取活化能或细胞色素 P450 芳烃羟化四面体中间体形成活化能的方法。本发明的方法可以在实用水平上快速预测 I 期代谢物的活化能，而无需在任何额外的 CYP450 和底物之间进行对接实验，也无需进行量子力学计算，从而使使用计算机开发新药物变得更加容易。同时，本发明还可以根据药物代谢的可能性，提出一种通过避免代谢物来提高药物生物利用度的策略。此外，本发明的方法提出了新的经验方法，也可以很容易地应用于各种化学反应的活化能，并使解释决定活化能的物理和化学因素成为可能。此外，根据本发明预测活化能，还可以预测 i) 代谢产物；ii) 代谢的相对速率；iii) 代谢的区域选择性；iv) 代谢抑制；v) 药物与药物之间的相互作用；以及 vi) 代谢产物的毒性。
• US8793078B2
  申请人：——

  公开号：US8793078B2

  公开（公告）日：2014-07-29