4-chloro-1-(2-chloro-2-phenylethyl)-6-(ethylthio)-1H-pyrazolo[3,4-d]pyrimidine | 679805-52-8

• 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-chloro-2-phenylethyl)-6-(ethylthio)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-Chloro-1-(2-chloro-2-phenylethyl)-6-(ethylthio)-1H-pyrazolo[3,4-d]pyrimidine；4-chloro-1-(2-chloro-2-phenylethyl)-6-ethylsulfanylpyrazolo[3,4-d]pyrimidine
• CAS: 679805-52-8
• 化学式: C₁₅H₁₄Cl₂N₄S
• 分子量: 353.275
• InChiKey: RULJKRRCJRXLGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  68.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(2-chloro-2-phenylethyl)-6-(ethylthio)-1H-pyrazolo[3,4-d]pyrimidine 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲苯 为溶剂， 反应 32.0h， 生成 4-[6-ethylsulfanyl-1-[(E)-2-phenylethenyl]pyrazolo[3,4-d]pyrimidin-4-yl]morpholine
  参考文献：
  名称：

  Pyrazolo[3,4-d]pyrimidines as Potent Antiproliferative and Proapoptotic Agents toward A431 and 8701-BC Cells in Culture via Inhibition of c-Src Phosphorylation

  摘要：

  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.

  DOI：

  10.1021/jm050603r
• 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 sodium hydroxide 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 8.17h， 生成 4-chloro-1-(2-chloro-2-phenylethyl)-6-(ethylthio)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  New pyrazolo[3,4-d]pyrimidines endowed with A431 antiproliferative activity and inhibitory properties of Src phosphorylation

  摘要：

  New 4-aminopyrazolo[3,4-d]pyrimidines bearing various substituents at the position I and 6, were synthesized. The new compounds showed antiproliferative activity toward A431 cells, were found to be inhibitors of Src phosphorylation, and induced apoptotic cell death. In particular, 2h was a better inhibitor of Src phosphorylation than the reference compound PP2. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.013

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。
• Identification and Biological Characterization of the Pyrazolo[3,4-d]pyrimidine Derivative SI388 Active as Src Inhibitor
  作者：Claudia Contadini、Claudia Cirotti、Anna Carbone、Mehrdad Norouzi、Annarita Cianciusi、Emmanuele Crespan、Cecilia Perini、Giovanni Maga、Daniela Barilà、Francesca Musumeci、Silvia Schenone

  DOI：10.3390/ph16070958

  日期：——

  including glioblastoma (GBM), has been extensively demonstrated. In this context, we started from our in-house library of pyrazolo[3,4-d]pyrimidines that are active as Src and/or Bcr-Abl TK inhibitors and performed a lead optimization study to discover a new generation derivative that is suitable for Src kinase targeting. We synthesized a library of 19 compounds, 2a-s. Among these, compound 2a (SI388)

  Src 是一种非受体酪氨酸激酶 (TK)，其与癌症（包括胶质母细胞瘤 (GBM)）的参与已被广泛证明。在这种情况下，我们从具有 Src 和/或 Bcr-Abl TK 抑制剂活性的吡唑并[3,4-d]嘧啶的内部库开始，进行了先导化合物优化研究，以发现适合的新一代衍生物用于 Src 激酶靶向。我们合成了 19 种化合物（2a-s）的库。其中，化合物 2a (SI388) 被确定为最有效的 Src 抑制剂。基于无细胞结果，我们研究了 SI388 在 2D 和 3D GBM 细胞模型中的作用。有趣的是，SI388 显着抑制 Src 激酶，从而影响细胞活力、致瘤性并增强癌细胞对电离辐射的敏感性。
• Identification of a Novel Pyrazolo[3,4-<i>d</i>]pyrimidine Able To Inhibit Cell Proliferation of a Human Osteogenic Sarcoma in Vitro and in a Xenograft Model in Mice
  作者：Fabrizio Manetti、Annalisa Santucci、Giada A. Locatelli、Giovanni Maga、Adriano Spreafico、Tommaso Serchi、Maurizio Orlandini、Giulia Bernardini、Nicola P. Caradonna、Andrea Spallarossa、Chiara Brullo、Silvia Schenone、Olga Bruno、Angelo Ranise、Francesco Bondavalli、Oskar Hoffmann、Mauro Bologna、Adriano Angelucci、Maurizio Botta

  DOI：10.1021/jm061449r

  日期：2007.11.1

  New pyrazolo[3,4-d]pyrimidines were synthesized and found to inhibit Src phosphorylation in a cell-free assay. Some of them significantly reduced the growth of human osteogenic sarcoma (SaOS-2) cells. The best compound, in terms of inhibitory properties toward both Src and SaOS-2 cells, was further investigated and found to reduce bone resorption when used to treat mouse osteoclasts, without interfering with normal osteoblast growth. Moreover, its metabolic stability prompted its study on a human SaOS-2 xenograft tumor model in nude mice, where the compound reduced significantly both the volume and weight of the tumor. These experimental findings make the new compound an interesting hit in the field of bone-related diseases.
• Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines
  作者：Silvia Schenone、Chiara Brullo、Olga Bruno、Francesco Bondavalli、Luisa Mosti、Giovanni Maga、Emmanuele Crespan、Fabio Carraro、Fabrizio Manetti、Cristina Tintori、Maurizio Botta

  DOI：10.1016/j.ejmech.2008.01.034

  日期：2008.12

  The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Pyrazolo[3,4-<i>d</i>]pyrimidines Endowed with Antiproliferative Activity on Ductal Infiltrating Carcinoma Cells
  作者：Fabio Carraro、Annalisa Pucci、Antonella Naldini、Silvia Schenone、Olga Bruno、Angelo Ranise、Francesco Bondavalli、Chiara Brullo、Paola Fossa、Giulia Menozzi、Luisa Mosti、Fabrizio Manetti、Maurizio Botta

  DOI：10.1021/jm034257u

  日期：2004.3.1

  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.