4-chloro-1-(2-phenylvinyl)-1H-pyrazolo[3,4-d]pyrimidine | 811412-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-chloro-1-(2-phenylvinyl)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-chloro-1-[(E)-2-phenylethenyl]pyrazolo[3,4-d]pyrimidine
• CAS: 811412-41-6
• 化学式: C₁₃H₉ClN₄
• 分子量: 256.694
• InChiKey: MRVFAXBPYHLGCG-VOTSOKGWSA-N

物化性质

• 熔点：
  139-140 °C
• 沸点：
  351.7±42.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  环己胺 、 4-chloro-1-(2-phenylvinyl)-1H-pyrazolo[3,4-d]pyrimidine 以 甲苯 为溶剂， 以80%的产率得到N-cyclohexyl-1-(2-phenylvinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Antiproliferative activity of new 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives toward the human epidermoid carcinoma A431 cell line

  摘要：

  Synthesis and biological evaluation of a new class of 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives are reported. A preliminary cellular assay system using the tumor cell line A431 responding to epidermal growth factor (EGF) for its growth, shows that the new compounds are potent inhibitors of cell growth. The inhibition of tumor cell proliferation is not associated with blockage of EGF receptor (EGFR), but substantially due to the interference with the signalling pathway at the level of Src tyrosine kinase and at the level of the downstream effector signal mitogen activated protein kinases (MAPKs), ERK1-2. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.07.010
• 作为产物：
  描述：

  5-氨基-1-(2-羟基-2-苯基乙基)-1H-吡唑-4-羧酸乙酯 在 三氯氧磷 作用下， 反应 20.0h， 生成 4-chloro-1-(2-phenylvinyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Pyrazolo[3,4-d]pyrimidines Endowed with Antiproliferative Activity on Ductal Infiltrating Carcinoma Cells

  摘要：

  Novel 1,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines are reported with preliminary in vitro activity data indicating that several of them are potent inhibitors (better than the reference compound) of Src phosphorylation of the breast cancer cells 8701-BC, known to overexpress Src. The ability of such compounds to significantly reduce 8701-BC cell proliferation suggests that this scaffold could be a promising lead for the development of antitumoral agents able to block Src phosphorylation of breast cancer cells.

  DOI：

  10.1021/jm034257u

文献信息

• 4-Substituted derivatives of pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine and uses thereof
  申请人：Bondavalli Francesco

  公开号：US20070010510A1

  公开（公告）日：2007-01-11

  4-Substituted derivatives of pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine are described. Compounds are active as antitumoural agents.

  本文描述了嘧唑并[3,4-d]嘧啶和吡咯并[2,3-d]嘧啶的4-取代衍生物。这些化合物作为抗肿瘤剂具有活性。
• Pyrazolo[3,4-<i>d</i>]pyrimidines as Potent Antiproliferative and Proapoptotic Agents toward A431 and 8701-BC Cells in Culture via Inhibition of c-Src Phosphorylation
  作者：Fabio Carraro、Antonella Naldini、Annalisa Pucci、Giada A. Locatelli、Giovanni Maga、Silvia Schenone、Olga Bruno、Angelo Ranise、Francesco Bondavalli、Chiara Brullo、Paola Fossa、Giulia Menozzi、Luisa Mosti、Michele Modugno、Cristina Tintori、Fabrizio Manetti、Maurizio Botta

  DOI：10.1021/jm050603r

  日期：2006.3.1

  We report here the synthesis of new pyrazolo[3,4-d]pyrimidine derivatives along with their biological properties as inhibitors of isolated Src and cell line proliferation (A431 and 8701-BC cells). Such compounds block the growth of cancer cells by interfering with the phosphorylation of Src, and they act as proapoptotic agents through the inhibition of the anti apoptotic gene BCL2. Several of them were found to be more active than the reference compound (1-(tert-butyl)-3-(4-chlorophenyl)-4-aminopyrazolo[3,4-d]pyrimidine, PP2) in inhibiting cell proliferation and in inducing apoptosis, and as active as PP2 in the inhibition of the phosphorylation of isolated Src. Moreover, molecular modeling simulations have been performed to hypothesize the way, at the molecular level, by which the inhibitors were able to act as antiproliferative agents.
• [EN] 4-SUBSTITUTED DERIVATIVES OF PYRAZOLO [3,4-d] PYRIMIDINE AND PYRROLO [2,3-d] PYRIMIDINE AND USES THEREOF<br/>[FR] DERIVES SUBSTITUES EN 4 DE PYRAZOLO[3,4-D]PYRIMIDINE ET PYRROLO[2,3-D]PYRIMIDINE ET UTILISATIONS ASSOCIEES
  申请人：UNIV SIENA

  公开号：WO2004106340A3

  公开（公告）日：2005-02-17
• A cascade screening approach for the identification of Bcr-Abl myristate pocket binders active against wild type and T315I mutant
  作者：Marco Radi、Ralf Schneider、Anna Lucia Fallacara、Lorenzo Botta、Emmanuele Crespan、Cristina Tintori、Giovanni Maga、Miroslava Kissova、Alessia Calgani、André Richters、Franesca Musumeci、Daniel Rauh、Silvia Schenone

  DOI：10.1016/j.bmcl.2016.06.051

  日期：2016.8

  The major clinical challenge in drug-resistant chronic myelogenous leukemia (CML) is currently represented by the Bcr-Abl T315I mutant, which is unresponsive to treatment with common first and second generation ATP-competitive tyrosine kinase inhibitors (TKIs). Allosteric inhibition of Bcr-Abl represent a new frontier in the fight against resistant leukemia and few candidates have been identified in the last few years. Among these, myristate pocket (MP) binders discovered by Novartis (e.g. GNF2/5) showed promising results, although they proved to be active against the T315I mutant only in combination with first and second generation ATP-competitive inhibitors. Here we used a cascade screening approach based on sequential fluorescence polarization (FP) screening, in silico docking/dynamics studies and kinetic-enzymatic studies to identify novel MP binders. A pyrazolo[3,4-d]pyrimidine derivative (6) has been identified as a promising allosteric inhibitor active on 32D leukemia cell lines (expressing Bcr-Abl WT and T315I) with no need of combination with any ATP-competitive inhibitor. (C) 2016 Elsevier Ltd. All rights reserved.
• 4-SUBSTITUTED DERIVATIVES OF PYRAZOLO ¬3,4-d PYRIMIDINE AND USES THEREOF
  申请人：UNIVERSITA DEGLI STUDI DI SIENA

  公开号：EP1638966B1

  公开（公告）日：2008-03-19