4-chloro-6-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine | 1204408-20-7

• 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: 4-chloro-6-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine
• CAS: 1204408-20-7
• 化学式: C₈H₁₀ClN₃
• 分子量: 183.64
• InChiKey: PSFUFEUHVPESOG-UHFFFAOYSA-N

物化性质

• 沸点：
  380.7±52.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-6-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine 在 盐酸 作用下， 以 乙醚 、 异丙醇 为溶剂， 生成 2-amino-N-(4-methoxyphenyl)-N,6-dimethyl-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：

  3-甲基己二酸 在 硫酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 14.0h， 生成 4-chloro-6-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine
  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

• BICYCLIC COMPOUNDS HAVING ANTIMITOTIC AND/OR ANTITUMOR ACTIVITY AND METHODS OF USE THEREOF
  申请人：Gangjee Aleem

  公开号：US20100010016A1

  公开（公告）日：2010-01-14

  The present invention provides bicyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

  本发明提供了具有抗有丝分裂活性、抗多药耐药活性（例如P-糖蛋白抑制作用）和抗肿瘤活性的双环化合物、药用可接受盐、前药、溶剂化合物和水合物，其能够抑制紫杉醇敏感和耐药肿瘤细胞。还提供了利用这些化合物治疗肿瘤细胞和抑制癌细胞有丝分裂的方法。
• Substituted pyrrolo, -furano, and cyclopentylpyrimidines having antimitotic and/or antitumor activity and methods of use thereof
  申请人：Gangjee Aleem

  公开号：US08946239B2

  公开（公告）日：2015-02-03

  The present invention provides substituted pyrrolo-, furano-, and cyclopentylpyrimidine bicyclic compounds of formula III, and 5,6-saturated and unsaturated and pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

  本发明提供了式III的取代吡咯烷基、呋喃基和环戊基嘧啶双环化合物，以及5,6-饱和和不饱和的药物可接受的盐、前药、溶剂合物和水合物，具有抗有丝分裂活性、抗多药耐药活性，例如P-糖蛋白抑制作用和抗肿瘤活性，并且抑制紫杉醇敏感和耐药肿瘤细胞。还提供了利用这些化合物治疗肿瘤细胞和抑制癌细胞有丝分裂的方法。
• Substituted Cyclopenta Pyrimidine Bicyclic Compounds Having Antitmitotic And/Or Antitumor Activity And Methods Of Use Thereof
  申请人：Gangjee Aleem

  公开号：US20140303188A1

  公开（公告）日：2014-10-09

  The present invention provides substituted cyclopenta and cyclopentyl pyrimidine bicyclic compounds of Formula III, and 5,6-saturated and unsaturated and pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

  本发明提供了式III的取代环戊基和环戊基嘧啶双环化合物，以及5,6-饱和和不饱和的药物可接受的盐、前药、溶剂化合物和水合物，具有抗有丝分裂活性、抗多药耐药活性，例如P-糖蛋白抑制作用和抗肿瘤活性，并且抑制紫杉醇敏感和耐药的肿瘤细胞。还提供了利用这些化合物治疗肿瘤细胞和抑制癌细胞有丝分裂的方法。
• Substituted Pyrrolo, -Furano, and Cyclopentylpyrimidines Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof
  申请人：Duquesne University of the Holy Spirit

  公开号：US20150105407A1

  公开（公告）日：2015-04-16

  The present invention provides substituted pyrrolo-, furano-, and cyclopentylpyrimidine bicyclic compounds of Formula III, and Formula IV, and pharmaceutically acceptable salts, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds and pharmaceutical compositions for treating tumor cells and inhibiting mitosis of cancerous cells.

  本发明提供了公式III和公式IV的取代吡咯烷基、呋喃基和环戊基嘧啶双环化合物，以及其药学上可接受的盐、溶剂合物和水合物，具有抗有丝分裂活性、抗多药耐药活性，例如P-糖蛋白抑制作用和抗肿瘤活性，并且可以抑制紫杉醇敏感和耐药的肿瘤细胞。还提供了使用这些化合物的方法和用于治疗肿瘤细胞和抑制癌细胞有丝分裂的制药组合物。
• PYRROLO[3,2-D]PYRIMIDINE-4-AMINE DERIVATIVES AND RELATED COMPOUNDS FOR THE TREATMENT OF CANCER
  申请人：Duquesne University of The Holy Spirit

  公开号：EP3130585A2

  公开（公告）日：2017-02-15

  The present invention relates to 4-amino, 4-oxy, 4-thio or 4-alkyl substituted pyrrolo[3,2d]pyrimidines, furo[3,2d]pyrimidines, cyclopenta[d]pyridines, pyrrolo[2,3d]pyrimidines and furo[2,3d]pyrimidines, pharmaceutically acceptable salts, solvates and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also disclosed are these compounds for use in a method of treating tumor cells and inhibiting mitosis of cancerous cells.

  本发明涉及 4-氨基、4-氧基、4-硫代或 4-烷基取代的吡咯并[3,2d]嘧啶、呋喃并[3,2d]嘧啶、环戊并[d]吡啶、吡咯并[2,3d]嘧啶和呋喃并[2,3d]嘧啶、其药学上可接受的盐类、溶液和水合物、这些化合物具有抗有丝分裂活性、抗多药耐药性活性（例如 P 糖蛋白抑制作用）和抗肿瘤活性，可抑制对紫杉醇敏感和耐药的肿瘤细胞。还公开了这些化合物用于治疗肿瘤细胞和抑制癌细胞有丝分裂的方法。