1-(2-羟基-2-苯基乙基)-6-(甲硫基)-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 | 679805-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 1-(2-羟基-2-苯基乙基)-6-(甲硫基)-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮
• 英文名称: 1-(2-hydroxy-2-phenylethyl)-6-(methylthio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
• 英文别名: 1-(2-Hydroxy-2-phenylethyl)-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one；1-(2-hydroxy-2-phenylethyl)-6-methylsulfanyl-5H-pyrazolo[3,4-d]pyrimidin-4-one
• CAS: 679805-49-3
• 化学式: C₁₄H₁₄N₄O₂S
• 分子量: 302.357
• InChiKey: VTMVNBQNCQXUBJ-UHFFFAOYSA-N

物化性质

• 熔点：
  208-209 °C(Solv: ethanol (64-17-5))
• 沸点：
  561.4±60.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-羟基-2-苯基乙基)-6-(甲硫基)-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 在 三氯氧磷 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 48.0h， 生成 N-[2-(3-chlorophenyl)-ethyl]-1-(2-chloro-2-phenylethyl)-6-(methylthio)-1H-pyrazolo[3,4-d]-pyrimidin-4-amine
  参考文献：
  名称：

  Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors

  摘要：

  Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies,; such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with K-i of about 2 mu M, while derivative 4a, derived from our internal library, showed a K-i of 0.9 mu M. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 44 having K(i)s of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of : the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines.

  DOI：

  10.1021/acs.jmedchem.5b00140
• 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 作用下， 以 四氢呋喃 为溶剂， 反应 24.17h， 生成 1-(2-羟基-2-苯基乙基)-6-(甲硫基)-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮
  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

• 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。
• Substituted pyrazolo[3,4-D]pyrimidines as anti-tumor agents
  申请人：Universita degli Studi di Siena

  公开号：US07589086B2

  公开（公告）日：2009-09-15

  The present invention provides a compound of pyrazolo[3,4-d]pyrimidine having the formula wherein: X=N; R=H, alkylthio, or aminoalkylthio; R1=NHcyclopropyl, NHC3H7, NHC4H9, N(CH2CH3)2, NHCH2CH2OC2H5, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, NHcyclohexyl, 1-hexahydroazepinyl, NHCH2C6H5, or NHCH2CH2C6H5; wherein R3=H, halogen, or alkyl and R5=Cl, Br or OH.

  本发明提供一种具有以下式的吡唑并[3,4-d]嘧啶化合物：其中： X = N; R = H，烷基硫或氨基烷基硫; R1 = NH环丙基，NHC3H7，NHC4H9，N（CH2CH3）2，NHCH2CH2OC2H5，1-吡咯烷基，1-哌啶基，4-吗啉基，NH环己基，1-六氢噁啉基，NHCH2C6H5或NHCH2CH2C6H5; 其中R3 = H，卤素或烷基，R5 = Cl，Br或OH。
• 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.
• 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.