N-[1(1R)-(4-methoxylphenyl)ethyl]-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[1(1R)-(4-methoxylphenyl)ethyl]-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
• 英文别名: N-[(1R)-1-(4-methoxyphenyl)ethyl]-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
• 化学式: C₁₈H₂₃N₃O
• 分子量: 297.4
• InChiKey: IEFFZWVVPHKQPV-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-(+)-1-(4-甲氧基苯)乙胺 在 盐酸 、 lithium aluminium tetrahydride 、 乙酸酐 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 为溶剂， 120.0 ℃ 、400.01 kPa 条件下， 反应 4.5h， 生成 N-[1(1R)-(4-methoxylphenyl)ethyl]-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
  参考文献：
  名称：

  基于结构的药物设计和体外代谢研究：发现N-（4-甲硫基苯基）-N，2-二甲基-环戊[d]嘧啶作为有效的微管靶向剂。

  摘要：

  我们报告了一系列的微管蛋白靶向剂，其中一些表现出有效的抗增殖活性。这些类似物的设计旨在通过改变4'-位的杂原子取代基，4-位氨基部分的碱性和构象限制条件来优化1的抗增殖活性。还合成了活性化合物的潜在代谢产物。一些化合物在MDA-MB-435黑色素瘤细胞中显示出抗增殖作用的一位数纳摩尔IC50值。特别是，在MDA-MB-435细胞中，S-甲基类似物3比1更有效（IC50 = 4.6 nM）。与人肝微粒体一起孵育3，表明3的S-甲基部分的主要代谢产物是甲基亚磺酰基，与类似物5一样。该代谢产物在MDA-MB-435细胞中与先导化合物1等价（IC50 = 7。9 nM）。确定分子模型和静电表面积以解释类似物的活性。大多数有效的化合物克服了多种耐药性机制，化合物3作为进一步SAR和临床前开发的先导化合物而出现。

  DOI：

  10.1016/j.bmc.2018.04.010

文献信息

• Cyclopenta[d]pyrimidines And Substituted Cyclopenta[d]pyrimidines As Antitubulin and Microtubule Targeting Agents, Monocyclic Pyrimidines As Tubulin Inhibitors, And Pyrrolopyrimidines As Targeted Antifolates And Tubulin and Multiple Receptor Tyrosine Kinase Inhibition And Antitumor Agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US20160304525A1

  公开（公告）日：2016-10-20

  The present invention provides a compound of Formula I, and salts thereof, and a pharmaceutical composition comprising a compound of Formula I: wherein R 1 is selected from the group consisting of and R 2 is an alkyl group having from one to ten carbon atoms, or wherein R 2 is selected from the group consisting of R 1 is an alkyl group having from one to ten carbon atoms; and R is H, or an alkyl group having from one to ten carbon atoms, and R 3 is H, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula V includes wherein R 3 is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.

  本发明提供了一种化合物I的盐，以及包括化合物I的药物组合物：其中R1选自以下组成的群体，R2是具有一到十个碳原子的烷基基团，或者R2选自以下组成的群体，R1是具有一到十个碳原子的烷基基团；R是H，或者具有一到十个碳原子的烷基基团，R3是H，具有一到十个碳原子的烷基基团，或者卤素。优选化合物V包括其中R3是卤素，最优选其中卤素是氯。还提供了使用这些化合物治疗癌症患者的方法。
• Cyclopenta[d]pyrimidines and substituted cyclopenta[d]pyrimidines as antitubulin and microtubule targeting agents, monocyclic pyrimidines as tubulin inhibitors, and pyrrolopyrimidines as targeted antifolates and tubulin and multiple receptor tyrosine kinase inhibition and antitumor agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US10239880B2

  公开（公告）日：2019-03-26

  The present invention provides a compound of Formula I, and salts thereof, and a pharmaceutical composition comprising a compound of Formula I: wherein R1 is selected from the group consisting of and R2 is an alkyl group having from one to ten carbon atoms, or wherein R2 is selected from the group consisting of R1 is an alkyl group having from one to ten carbon atoms; and R is H, or an alkyl group having from one to ten carbon atoms, and R3 is H, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula V includes wherein R3 is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.

  本发明提供了一种式 I 的化合物及其盐类，以及一种包含式 I 化合物的药物组合物： 其中 R1 选自以下组成的组 和 R2 是具有 1 至 10 个碳原子的烷基，或 其中 R2 选自以下组成的组 R1 是具有一至十个碳原子的烷基；R 是 H 或具有一至十个碳原子的烷基，R3 是 H、具有一至十个碳原子的烷基或卤素。其中 R3 是卤素，最优选的是卤素是氯。还提供了用这些化合物治疗癌症患者的方法。
• Cyclopenta[d]pyrimidines and substituted cyclopenta[d]pyrimidines as antitubulin and microtubule targeting agents, monocyclic pyrimidines as tubulin inhibitors, and pyrrolopyrimidines as targeted antifolates and tubulin and multiple receptor tyrosine kinase inhibitor and antitumor agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US11124520B2

  公开（公告）日：2021-09-21

  The present invention provides a compound of Formula III, and salts thereof, and a pharmaceutical composition comprising a compound of Formula III: wherein R1 is selected from the group consisting of: wherein R2 is H or an alkyl group having from one to ten carbon atoms; R3 is H or an alkyl group having from one to ten carbon atoms; and R4 is H or an alkyl group having from one to ten carbon atoms. Methods of treating a patient with cancer with these compounds are also provided.

  本发明提供了一种式 III 的化合物及其盐类，以及一种包含式 III 化合物的药物组合物： 其中 R1 选自以下组成的组 在其中 R2 是 H 或具有一至十个碳原子的烷基； R3 是 H 或具有一至十个碳原子的烷基；以及 R4 是 H 或具有一至十个碳原子的烷基。还提供了用这些化合物治疗癌症患者的方法。
• [EN] CYCLOPENTA[D]PYRIMIDINES AND SUBSTITUTED CYCLOPENTA[D]PYRIMIDINES AS ANTITUBULIN AND MICROTUBULE TARGETING AGENTS, MONOCYCLIC PYRIMIDINES AS TUBULIN INHIBITORS, AND PYRROLOPYRIMIDINES AS TARGETED ANTIFOLATES AND TUBULIN AND MULTIPLE RECEPTOR TYROSINE KINASE INHIBITION AND ANTITUMOR AGENTS<br/>[FR] CYCLOPENTA[D]PYRIMIDINES ET CYCLOPENTA[D]PYRIMIDINES SUBSTITUÉES UTILISÉES EN TANT QU'AGENTS ANTITUBULINE ET DE CIBLAGE DE MICROTUBULES, PYRIMIDINES MONOCYCLIQUES UTILISÉES EN TANT QU'INHIBITEURS DE TUBULINE, ET PYRROLOPYRIMIDINES UTILISÉES EN TANT QU'ANTIFOLATES CIBLÉS ET AGENTS ANTITUMORAUX ET D'INHIBITION DE TUBULINE ET DE TYROSINE KINASE À RÉCEPTEURS MULTIPLES
  申请人：UNIV HOLY GHOST DUQUESNE

  公开号：WO2016168637A2

  公开（公告）日：2016-10-20

  The present invention provides a pyrimidine compound and salts thereof, and substituted pyrimidine compounds and salts thereof, and a pharmaceutical composition comprising these compounds. Methods of treating a patient with cancer with these compounds are also provided.
• Structure based drug design and in vitro metabolism study: Discovery of N-(4-methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a potent microtubule targeting agent
  作者：Weiguo Xiang、Shruti Choudhary、Ernest Hamel、Susan L. Mooberry、Aleem Gangjee

  DOI：10.1016/j.bmc.2018.04.010

  日期：2018.5

  We report a series of tubulin targeting agents, some of which demonstrate potent antiproliferative activities. These analogs were designed to optimize the antiproliferative activity of 1 by varying the heteroatom substituent at the 4'-position, the basicity of the 4-position amino moiety, and conformational restriction. The potential metabolites of the active compounds were also synthesized. Some compounds

  我们报告了一系列的微管蛋白靶向剂，其中一些表现出有效的抗增殖活性。这些类似物的设计旨在通过改变4'-位的杂原子取代基，4-位氨基部分的碱性和构象限制条件来优化1的抗增殖活性。还合成了活性化合物的潜在代谢产物。一些化合物在MDA-MB-435黑色素瘤细胞中显示出抗增殖作用的一位数纳摩尔IC50值。特别是，在MDA-MB-435细胞中，S-甲基类似物3比1更有效（IC50 = 4.6 nM）。与人肝微粒体一起孵育3，表明3的S-甲基部分的主要代谢产物是甲基亚磺酰基，与类似物5一样。该代谢产物在MDA-MB-435细胞中与先导化合物1等价（IC50 = 7。9 nM）。确定分子模型和静电表面积以解释类似物的活性。大多数有效的化合物克服了多种耐药性机制，化合物3作为进一步SAR和临床前开发的先导化合物而出现。