1-(2-chloro-2-phenylethyl)-6-(methylthio)-4-(piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine | 679805-32-4

• 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: 1-(2-chloro-2-phenylethyl)-6-(methylthio)-4-(piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 1-(2-chloro-2-phenylethyl)-6-methylsulfanyl-4-piperidin-1-ylpyrazolo[3,4-d]pyrimidine
• CAS: 679805-32-4
• 化学式: C₁₉H₂₂ClN₅S
• 分子量: 387.936
• InChiKey: RLTNCWZNNOAYJB-UHFFFAOYSA-N

物化性质

• 熔点：
  94-95 °C
• 沸点：
  595.6±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-2-phenylethyl)-6-(methylthio)-4-(piperidin-1-yl)-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， 反应 8.0h， 以67%的产率得到6-methylsulfanyl-1-[(E)-2-phenylethenyl]-4-piperidin-1-ylpyrazolo[3,4-d]pyrimidine
  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 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 氯仿 、 甲苯 为溶剂， 反应 52.17h， 生成 1-(2-chloro-2-phenylethyl)-6-(methylthio)-4-(piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  1-（2-氯-2-苯基乙基）-6-甲硫基-1H-吡唑并[3,4-d]嘧啶4-氨基取代基的合成及其生物学评价。

  摘要：

  合成了一系列新的4-氨基-6-甲硫基-1H-吡唑并[3,4-d]嘧啶（2a-m），在N1位带有2-氯-2-苯基乙基链。测量了这些化合物对A1腺苷受体（A1AR）的亲和力。化合物显示出较差的亲和力。通过2a，2d，2g获得了更有趣的结果，该结果显示了对上皮生长因子（EGF）刺激的A-431细胞系的细胞增殖和EGF受体酪氨酸激酶（EGFR-TK）磷酸化的抑制活性。

  DOI：

  10.1016/j.ejmech.2003.11.007

文献信息

• Synthesis of 1-(2-chloro-2-phenylethyl)-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines 4-amino substituted and their biological evaluation
  作者：Silvia Schenone、Olga Bruno、Francesco Bondavalli、Angelo Ranise、Luisa Mosti、Giulia Menozzi、Paola Fossa、Fabrizio Manetti、Lucia Morbidelli、Letizia Trincavelli、Claudia Martini、Antonio Lucacchini

  DOI：10.1016/j.ejmech.2003.11.007

  日期：2004.2

  A new series of 4-amino-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines (2a-m) bearing the 2-chloro-2-phenylethyl chain at the N1 position, has been synthesized. The affinity of these compounds for A1 adenosine receptor (A1AR) was measured. The compounds showed poor affinity. A more interesting result was obtained by 2a, 2d, 2g, which demonstrated inhibitory activity on cell proliferation of the A-431 cell

  合成了一系列新的4-氨基-6-甲硫基-1H-吡唑并[3,4-d]嘧啶（2a-m），在N1位带有2-氯-2-苯基乙基链。测量了这些化合物对A1腺苷受体（A1AR）的亲和力。化合物显示出较差的亲和力。通过2a，2d，2g获得了更有趣的结果，该结果显示了对上皮生长因子（EGF）刺激的A-431细胞系的细胞增殖和EGF受体酪氨酸激酶（EGFR-TK）磷酸化的抑制活性。
• New pyrazolo[3,4-d]pyrimidines endowed with A431 antiproliferative activity and inhibitory properties of Src phosphorylation
  作者：S. Schenone、O. Bruno、A. Ranise、F. Bondavalli、C. Brullo、P. Fossa、L. Mosti、G. Menozzi、F. Carraro、A. Naldini、C. Bernini、F. Manetti、M. Botta

  DOI：10.1016/j.bmcl.2004.03.013

  日期：2004.5

  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.
• 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.
• [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
• 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.