2,2-dimethyl-N-(4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indol-2-yl)propanamide | 1133824-76-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,2-dimethyl-N-(4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indol-2-yl)propanamide
• 英文别名: 2,2-Dimethyl-N-(4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indol-2-yl)propanamide；2,2-dimethyl-N-(4-oxo-3,9-dihydropyrimido[4,5-b]indol-2-yl)propanamide
• CAS: 1133824-76-6
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: YZBOQKCQVLEIRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  86.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-N-(4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indol-2-yl)propanamide 在 盐酸 、 三氯氧磷 作用下， 以 水 、 异丙醇 为溶剂， 反应 76.0h， 生成 N-{4-[(4-methoxyphenyl)(methyl)amino]-9H-pyrimido[4,5-b]indol-2-yl}-2,2-dimethylpropanamide
  参考文献：
  名称：

  Synthesis of N4-(substituted phenyl)-N4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells

  摘要：

  A series of fourteen N-4-(substituted phenyl)-N-4-alkyl/clesalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI(50) values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [H-3]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the 0111 isotype of tubulin, which have been associated with clinical drug resistance. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.010
• 作为产物：
  描述：

  2-amino-3,5,6,7,8,9-hexahydro-4H-pyrimido[4,5-b]indol-4-one 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成 2,2-dimethyl-N-(4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indol-2-yl)propanamide
  参考文献：
  名称：

  Synthesis of N4-(substituted phenyl)-N4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells

  摘要：

  A series of fourteen N-4-(substituted phenyl)-N-4-alkyl/clesalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI(50) values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [H-3]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the 0111 isotype of tubulin, which have been associated with clinical drug resistance. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.010

文献信息

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

  公开号：US20090082374A1

  公开（公告）日：2009-03-26

  The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, 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.

  本发明提供了三环化合物、药学上可接受的盐、前药、溶剂或其水合物，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。同时，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。
• Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof
  申请人：Duquesne University of the Holy Spirit

  公开号：US07982035B2

  公开（公告）日：2011-07-19

  The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, 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.

  本发明提供了三环化合物、药学上可接受的盐、前药、溶剂化合物或水合物，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。同时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。
• Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof
  申请人：Gangjee Aleem

  公开号：US20130096146A1

  公开（公告）日：2013-04-18

  The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, 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.

  本发明提供了三环化合物，其药物可接受的盐，前药，溶剂化合物或其水合物，具有抗有丝分裂活性，抗多药耐药活性，例如P-糖蛋白抑制，以及抗肿瘤活性，且能够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。
• Tricyclic compounds having antimitotic and/or antitumor activity and method of use thereof
  申请人：Duquesne University of the Holy Spirit

  公开号：US10414777B2

  公开（公告）日：2019-09-17

  The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, 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.

  本发明提供了三环化合物、其药学上可接受的盐、原药、溶液剂或水合物，它们具有抗有丝分裂活性、抗多种药物耐药性活性（例如 P 糖蛋白抑制）和抗肿瘤活性，可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。
• TRICYCLIC COMPOUNDS HAVING ANTIMITOTIC AND/OR ANTITUMOR ACTIVITY AND METHOD OF USE THEREOF
  申请人：Duquesne University of the Holy Spirit

  公开号：US20180127434A1

  公开（公告）日：2018-05-10

  The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, 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.