2,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one | 1452392-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one
• 英文别名: 2,5-Dimethyl-3,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one；2,5-dimethyl-3,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one
• CAS: 1452392-68-5
• 化学式: C₉H₁₂N₂O
• 分子量: 164.207
• InChiKey: YBPVNZUNWWGTSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one 在 盐酸 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 生成 N-(4-methoxyphenyl)-N,2,5-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium chloride
  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
• 作为产物：
  描述：

  methyl 2-diazo-3-oxoheptanoate 在 rhodium(II) acetate dimer 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 3.0h， 生成 2,5-dimethyl-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one
  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