N-(4-bromobenzyl)-2-chloro-9-isopropyl-9H-purin-6-amine | 294647-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N-(4-bromobenzyl)-2-chloro-9-isopropyl-9H-purin-6-amine
• 英文别名: N-[(4-bromophenyl)methyl]-2-chloro-9-propan-2-ylpurin-6-amine
• CAS: 294647-89-5
• 化学式: C₁₅H₁₅BrClN₅
• 分子量: 380.675
• InChiKey: MTBHLDMWSYMTFK-UHFFFAOYSA-N

物化性质

• 熔点：
  136-140 °C
• 沸点：
  475.6±50.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)
• pKa：
  0.30±0.10 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-bromobenzyl)-2-chloro-9-isopropyl-9H-purin-6-amine 在 盐酸羟胺 、 palladium diacetate 、 三(邻甲基苯基)磷 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.0h， 生成 (E)-N-hydroxy-3-(4-(((9-isopropyl-2-(pyrrolidin-1-yl)-9H-purin-6-yl)amino)methyl)phenyl)acrylamide
  参考文献：
  名称：

  发现新型9H-嘌呤衍生物作为HDAC1和CDK2的双重抑制剂。

  摘要：

  HDAC和CDK抑制剂已被证明在抑制癌细胞增殖和诱导细胞凋亡方面具有协同作用。在这项工作中，我们将HDACs和CDKs抑制剂的药效基团整合到一个分子中，以设计和合成一系列作为HDAC / CDK双重抑制剂的嘌呤衍生物。铅化合物6d表现出良好的HDAC1和CDK2抑制活性，IC 50值分别为5.8和56 nM，在体外对几种癌细胞表现出诱人的效力。这项工作可能会导致发现新型支架和潜在的双重HDAC / CDK抑制剂。

  DOI：

  10.1016/j.bmcl.2019.06.059
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-(4-bromobenzyl)-2-chloro-9-isopropyl-9H-purin-6-amine
  参考文献：
  名称：

  发现新型9H-嘌呤衍生物作为HDAC1和CDK2的双重抑制剂。

  摘要：

  HDAC和CDK抑制剂已被证明在抑制癌细胞增殖和诱导细胞凋亡方面具有协同作用。在这项工作中，我们将HDACs和CDKs抑制剂的药效基团整合到一个分子中，以设计和合成一系列作为HDAC / CDK双重抑制剂的嘌呤衍生物。铅化合物6d表现出良好的HDAC1和CDK2抑制活性，IC 50值分别为5.8和56 nM，在体外对几种癌细胞表现出诱人的效力。这项工作可能会导致发现新型支架和潜在的双重HDAC / CDK抑制剂。

  DOI：

  10.1016/j.bmcl.2019.06.059

文献信息

• Synthesis and activity of 2,6,9-trisubstituted purines
  作者：Steven R. Schow、Richard L. Mackman、Cheri L. Blum、Eric Brooks、Amy G. Horsma、Alison Joly、Suresh S. Kerwar、Gavin Lee、Dov Shiffman、Marek G. Nelson、Xingbo Wang、Michael M. Wick、Xiaoming Zhang、Robert T. Lum

  DOI：10.1016/s0960-894x(97)10076-2

  日期：1997.11

  The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented. (C) 1997 Elsevier Science Ltd.
• Biaryl purine derivatives as potent antiproliferative agents: Inhibitors of cyclin dependent kinases. Part I
  作者：Michael P. Trova、Keith D. Barnes、Curt Barford、Travis Benanti、Mark Bielaska、Lori Burry、John M. Lehman、Christine Murphy、Harold O’Grady、Denise Peace、Susan Salamone、Jennifer Smith、Patricia Snider、Joseph Toporowski、Steven Tregay、Alison Wilson、Michael Wyle、Xiaozhang Zheng、Thomas D. Friedrich

  DOI：10.1016/j.bmcl.2009.10.025

  日期：2009.12

  The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2). (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] 6-SUBSTITUTED BIARYL PURINE DERIVATIVES AS POTENT CYCLIN/CDK INHIBITORS AND ANTIPROLIFERATIVE AGENTS<br/>[FR] DERIVES DE PURINE DIARYLE SUBSTITUEE EN 6 UTILISES COMME INHIBITEURS PUISSANTS DE KINASE DEPENDANTE DES CYCLINES ET COMME AGENTS ANTIPROLIFERATIFS
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2000055161A1

  公开（公告）日：2000-09-21

  The present invention is directed to 2,6,9-trisubstituted purines cellular proliferation. Processes of preparing such compounds are also disclosed.
• [EN] NITROGEN SUBSTITUTED BIARYL PURINE DERIVATIVES AS POTENT ANTIPROLIFERATIVE AGENTS<br/>[FR] DERIVES DE PURINE BIARYLE A SUBSTITUTION AZOTE UTILES EN TANT QUE PUISSANTS AGENTS ANTIPROLIFERATIFS
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2003022219A2

  公开（公告）日：2003-03-20

  The compounds of the present invention are 2,6,9-trisubstituted purine derivatives which are inhibitors of cyclin/cdk complexes. The compounds of the current invention also are potent inhibitors of human cellular proliferation. As such, the compounds of the present invention constitute pharmaceutical compositions with a pharmaceutically acceptable carrier. Such compounds are useful in treating a disorder mediated by elevated levels of cell proliferation in a mammal compared to a healthy mammal by administering to such mammal an effective amount of the compound. Examples of the compounds of the present invention are represented by the following chemical structures; with X, Y, D, Q, V, A, R1, R2, R3, R4, and n1 defined herein.
• [EN] HETEROCYCLE SUBSTITUTED PURINE DERIVATIVES AS POTENT ANTIPROLIFERATIVE AGENTS<br/>[FR] DERIVES DE PURINE A SUBSTITUTION HETEROCYCLE UTILES EN TANT QUE PUISSANTS AGENTS ANTIPROLIFERATIFS
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2003022805A2

  公开（公告）日：2003-03-20

  The compounds of the present invention are 2,6,9-trisubstituted purine derivatives which are inhibitors of cyclin/cdk complexes. The compounds of the current invention also are potent inhibitors of human cellular proliferation. As such, the compounds of the present invention constitute pharmaceutical compositions with a pharmaceutically acceptable carrier. Such compounds are useful in treating a disorder mediated by elevated levels of cell proliferation in a mammal compared to a healthy mammal by administering to such mammal an effective amount of the compound. Examples of the compounds of the present invention are represented by the following chemical structures (I) and (II) with Y, V, A, R1, R2, R3, R4, R7, and n1 defined herein.