4-N-(4-methoxyphenyl)-4-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine | 1452669-66-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-N-(4-methoxyphenyl)-4-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine
• CAS: 1452669-66-7
• 化学式: C₁₅H₁₈N₄O
• 分子量: 270.334
• InChiKey: KAIOANMKTZOQEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-6,7-二氢-5H-环戊[d]嘧啶-4-醇 在 盐酸 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 生成 4-N-(4-methoxyphenyl)-4-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Structure–Activity Relationship and in Vitro and in Vivo Evaluation of the Potent Cytotoxic Anti-microtubule Agent N-(4-Methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium Chloride and Its Analogues As Antitumor Agents

  摘要：

  A series of 21 substituted cyclopenta[d]pyrimidines were synthesized as an extension of our discovery of the parent compound (+/-)-1 center dot HCl as an anti-microtubule agent. The structure activity relationship indicates that the N-methyl and a 4N-methoxy groups appear important for potent activity. In addition, the 6-substituent in the parent analogue is not necessary for activity. The most potent compound 30. HCl was a one to two digit nanomolar inhibitor of most tumor cell proliferations and was up to 7-fold more potent than the parent compound (+/-)-1 center dot HCl. In addition, 30 center dot HCl inhibited cancer cell proliferation regardless of Pgp or beta III-tubulin status, both of which are known to cause clinical resistance to several antitubulin agents. In vivo efficacy of 30 center dot HCl was demonstrated against a triple negative breast cancer xenograft mouse model. Compound 30 center dot HCl is water-soluble and easily synthesized and serves as a lead compound for further preclinical evaluation as an

  DOI：

  10.1021/jm400639z

文献信息

• Structure–Activity Relationship and in Vitro and in Vivo Evaluation of the Potent Cytotoxic Anti-microtubule Agent <i>N</i>-(4-Methoxyphenyl)-<i>N</i>,2,6-trimethyl-6,7-dihydro-5<i>H</i>-cyclopenta[<i>d</i>]pyrimidin-4-aminium Chloride and Its Analogues As Antitumor Agents
  作者：Aleem Gangjee、Ying Zhao、Sudhir Raghavan、Cristina C. Rohena、Susan L. Mooberry、Ernest Hamel

  DOI：10.1021/jm400639z

  日期：2013.9.12

  A series of 21 substituted cyclopenta[d]pyrimidines were synthesized as an extension of our discovery of the parent compound (+/-)-1 center dot HCl as an anti-microtubule agent. The structure activity relationship indicates that the N-methyl and a 4N-methoxy groups appear important for potent activity. In addition, the 6-substituent in the parent analogue is not necessary for activity. The most potent compound 30. HCl was a one to two digit nanomolar inhibitor of most tumor cell proliferations and was up to 7-fold more potent than the parent compound (+/-)-1 center dot HCl. In addition, 30 center dot HCl inhibited cancer cell proliferation regardless of Pgp or beta III-tubulin status, both of which are known to cause clinical resistance to several antitubulin agents. In vivo efficacy of 30 center dot HCl was demonstrated against a triple negative breast cancer xenograft mouse model. Compound 30 center dot HCl is water-soluble and easily synthesized and serves as a lead compound for further preclinical evaluation as an