2-Amino-4-(3-bromoanilino)indolo[2,3-d]pyrimidine

• 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-Amino-4-(3-bromoanilino)indolo[2,3-d]pyrimidine
• 英文别名: 4-N-(3-bromophenyl)-9H-pyrimido[4,5-b]indole-2,4-diamine
• 化学式: C₁₆H₁₂BrN₅
• 分子量: 354.209
• InChiKey: NOUNTOCKLNSANP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-{4-[(3-bromophenyl)amino]-9H-pyrimido[4,5-b]indol-2-yl}-2,2-dimethylpropanamide 在 异丙醇 、 sodium hydroxide 作用下， 反应 14.0h， 以76%的产率得到2-Amino-4-(3-bromoanilino)indolo[2,3-d]pyrimidine
  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

• Tyrosine Kinase Inhibitors. 16. 6,5,6-Tricyclic Benzothieno[3,2-<i>d</i>]pyrimidines and Pyrimido[5,4-<i>b</i>]- and -[4,5-<i>b</i>]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase
  作者：H. D. Hollis Showalter、Alexander J. Bridges、Hairong Zhou、Anthony D. Sercel、Amy McMichael、David W. Fry

  DOI：10.1021/jm9903949

  日期：1999.12.1

  Investigation of 4-position side chains in the indolopyrimidines confirmed that m-bromoaniline was an optimal substituent for potency. Investigation of substitution within the C-(benzo)ring of benzothienopyrimidines confirmed that introduction of an extra ring can change sharply the effects of substituents when compared to similar bicyclic nuclei, and only two substituents were found which even moderately

  据报道，基本的苯胺基嘧啶药效基团的几种精制方法是表皮生长因子受体（EGFr）酪氨酸激酶的有效和选择性抑制剂。本文报道了一系列抑制剂，其中一些6,5-双环杂芳族系统通过其C-2和C-3位置与该苯胺嘧啶药效团融合。尽管产生的三轮车并未产生某些（5/6），6,6-双环系统的巨大效能，但最好的三轮车的EGFr TK的IC（50）约为1 nM。对吲哚并嘧啶中4-位侧链的研究证实，间溴苯胺是效力的最佳取代基。
• Tricyclic compounds capable of inhibiting tyrosine kinases of the
  申请人：Warner-Lambert Company

  公开号：US05679683A1

  公开（公告）日：1997-10-21

  Novel 4-substituted amino benzothieno\x9b3,2-d!pyrimidine and 4-substituted amino\x9b2,3-d!pyrimidine inhibitors of epidermal growth factor receptor family of tyrosine kinases are described, as well as pharmaceutical compositions of the same, which are useful in treating proliferative diseases such as cancer, synovial pannus invasion in arthritis, psoriasis, vascular restenosis and angiogenesis and additionally useful in the treatment of pancreatitis and kidney disease as well as a contraceptive agent.

  描述了一种新型的4-取代氨基苯并噻吩\9b3,2-d!嘧啶和4-取代氨基\9b2,3-d!嘧啶表皮生长因子受体家族的酪氨酸激酶抑制剂，以及相应的药物组合物，用于治疗增殖性疾病，如癌症、关节炎中的滑膜潘纳斯侵袭、牛皮癣、血管再狭窄和血管生成，此外还可用于胰腺炎和肾病的治疗，以及避孕剂。
• Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
  申请人：Warner Lambert Company

  公开号：US06596726B1

  公开（公告）日：2003-07-22

  Described are compounds of the following formula and a method of inhibiting epidermal growth factor by treating, with an effective inhibiting amount, a mammal, in need thereof, a compound of the formula: wherein the formula terms are described in the specification and wherein the members in the aforementioned structure are defined in the specification.

  本文描述了以下公式的化合物以及通过使用有效的抑制量处理需要该化合物的哺乳动物来抑制表皮生长因子的方法：其中公式术语在说明书中描述，上述结构中的成员在说明书中定义。
• 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：US09045489B2

  公开（公告）日：2015-06-02

  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.

  本发明提供三环化合物，其药学上可接受的盐，前药，溶剂化物或水合物，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，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。
• 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。