N-[[4-(5-溴嘧啶-2-基)氧基-3-甲基苯基]氨基甲酰]-2-二甲基氨基苯甲酰胺 | 134742-19-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[[4-(5-溴嘧啶-2-基)氧基-3-甲基苯基]氨基甲酰]-2-二甲基氨基苯甲酰胺
• 英文名称: N-[4-(5-bromo-2-pyrimidinyloxy)-3methylphenyl]-N'-[2-(dimethylamino)benzoyl]urea
• 英文别名: N-(((4-((5-Bromo-2-pyrimidinyl)oxy)-3-methylphenyl)amino)carbonyl)-2-(dimethylamino)benzamide；N-[[4-(5-bromopyrimidin-2-yl)oxy-3-methylphenyl]carbamoyl]-2-(dimethylamino)benzamide
• CAS: 134742-19-1
• 化学式: C₂₁H₂₀BrN₅O₃
• 分子量: 470.325
• InChiKey: JNGQUJZDVFZPEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  6

ADMET

代谢

N-({4-[(5-溴嘧啶-2-基)氧基]-3-甲基苯基}氨基甲酰基)-2-(二甲基氨基)苯甲酰胺已知的人类代谢物包括mmBPU。

N-({4-[(5-bromopyrimidin-2-yl)oxy]-3-methylphenyl}carbamoyl)-2-(dimethylamino)benzamide has known human metabolites that include mmBPU.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  N-[[4-(5-溴嘧啶-2-基)氧基-3-甲基苯基]氨基甲酰]-2-二甲基氨基苯甲酰胺 、 盐酸 以 乙醚 、 二氯甲烷 为溶剂， 生成 N-[4-(5-bromo-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)benzoyl]urea.hydrochloride
  参考文献：
  名称：

  Substituted benzoylurea compounds or their salts, processes for their

  摘要：

  化合物的结构式为(I)：##STR1##其中R.sup.1是氢原子，卤原子或硝基基团，R.sup.2和R.sup.3中的每一个是氢原子，烷基，--COR.sup.6（其中R.sup.6是烷基或烷氧基）或--SO.sub.2R.sup.6（其中R.sup.6如上所定义），或者R.sup.2和R.sup.3与相邻的氮原子一起形成杂环环，R.sup.4是卤原子，取代或未取代的烷基，取代或未取代的烷氧基，取代或未取代的烷硫基或硝基，R.sup.5是卤原子，硝基或取代或未取代的烷基，或其盐。

  公开号：

  US05102884A1
• 作为产物：
  描述：

  2-(二甲氨基)苯甲酰胺 、 4-(5-bromo-2-pyrimidinyloxy)-3-methylphenyl isocyanate 以 甲苯 为溶剂， 反应 4.0h， 生成 N-[[4-(5-溴嘧啶-2-基)氧基-3-甲基苯基]氨基甲酰]-2-二甲基氨基苯甲酰胺
  参考文献：
  名称：

  Substituted benzoylurea compounds or their salts, processes for their

  摘要：

  化合物的结构式为(I)：##STR1##其中R.sup.1是氢原子，卤原子或硝基基团，R.sup.2和R.sup.3中的每一个是氢原子，烷基，--COR.sup.6（其中R.sup.6是烷基或烷氧基）或--SO.sub.2R.sup.6（其中R.sup.6如上所定义），或者R.sup.2和R.sup.3与相邻的氮原子一起形成杂环环，R.sup.4是卤原子，取代或未取代的烷基，取代或未取代的烷氧基，取代或未取代的烷硫基或硝基，R.sup.5是卤原子，硝基或取代或未取代的烷基，或其盐。

  公开号：

  US05102884A1

文献信息

• Substituted benzoylurea compounds or their salts, processes for their production and antitumour compositions containing them
  申请人：ISHIHARA SANGYO KAISHA, LTD.

  公开号：EP0413977A2

  公开（公告）日：1991-02-27

  A substituted benzoylurea compound of the formula (I): wherein R¹ is a hydrogen atom, a halogen atom or a nitro group, each of R² and R³ is a hydrogen atom, an alkyl group, -COR⁶ (wherein R⁶ is an alkyl group or an alkoxy group) or -SO₂R⁶ (wherein R⁶ is as defined above), or R² and R³ may form together with the adjacent nitrogen atom a heterocyclic ring, R⁴ is a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group or a nitro group, and R⁵ is a halogen atom, a nitro group or a substituted or unsubstituted alkyl group, or its salt.

  化合物的化学式（I）为：其中R¹是氢原子、卤素原子或硝基基团，R²和R³分别是氢原子、烷基、-COR⁶（其中R⁶是烷基或烷氧基）或-SO₂R⁶（其中R⁶如上所定义），或R²和R³可以与相邻的氮原子形成杂环环，R⁴是卤素原子、取代或未取代的烷基、取代或未取代的烷氧基、取代或未取代的烷硫基或硝基，R⁵是卤素原子、硝基或取代或未取代的烷基，或其盐。
• 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。
• Synthesis and antitumor evaluation of benzoylphenylurea analogs
  作者：Hallur Gurulingappa、Maria L Amador、Ming Zhao、Michelle A Rudek、Manuel Hidalgo、Saeed R Khan

  DOI：10.1016/j.bmcl.2004.02.019

  日期：2004.5

  Novel series of benzoylphenylurea analogs 7-10 were prepared and evaluated for in vitro cytotoxic activity against a panel of eight different human cancer cell lines. A very interesting inhibition profile against BxPC3, Mia-Paca, and Hep2 cells with compound 10 has been observed. Compounds 8 and 9 showed the significant cytotoxicity in Hep2 cells. All cell lines were resistant to compound 7. (C) 2004 Elsevier Ltd. All rights reserved.
• JPH0429979A
  申请人：——

  公开号：JPH0429979A

  公开（公告）日：1992-01-31
• Weak base salts
  申请人：Yalkowsky H. Samuel

  公开号：US20070043070A1

  公开（公告）日：2007-02-22

  Pharmaceutical compositions comprising a salt of a weak base compound of formula: wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms; n is a positive integer of less than 4; Y is hydrogen, chlorine, nitro, methyl, ethyl or oxy-chloro; R is hydrogen, alkylaminocarbonyl wherein the alkyl group has from 3 to 6 carbon atoms or an alkyl group having from 1 to 8 carbons and R2 is 4-thiazolyl, NHCOOR1 wherein R, is aliphatic hydrocarbon of less than 7 carbon atoms, or an alkyl group of less than 7 carbon atoms; one or more free acids; and optional pharmaceutical additives are provided.