2-[(4-Methoxyphenyl)-methylsulfanylmethylidene]propanedinitrile | 111510-02-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[(4-Methoxyphenyl)-methylsulfanylmethylidene]propanedinitrile
• CAS: 111510-02-2
• 化学式: C₁₂H₁₀N₂OS
• 分子量: 230.29
• InChiKey: XTYPTQPSQXNXJM-UHFFFAOYSA-N

物化性质

• 熔点：
  95 °C(Solv: methanol (67-56-1))
• 沸点：
  367.5±42.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(4-Methoxyphenyl)-methylsulfanylmethylidene]propanedinitrile 在 三溴化硼 、 一水合肼 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 25.0h， 生成 4-(3-chloro-phenylamino)-3-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Use of a Pharmacophore Model for the Design of EGF-R Tyrosine Kinase Inhibitors:  4-(Phenylamino)pyrazolo[3,4-d]pyrimidines

  摘要：

  In the course of the random screening of a pool of CIBA chemicals, the two pyrazolopyrimidines 1 and 2 have been identified as fairly potent inhibitors of the EGF-R tyrosine kinase. Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGF-R protein tyrosine kinase (PTK), the class of the pyrazolo[3,4-d]pyrimidines was then optimized in an interactive process leading to a series of 4-(phenylamino)-1H-pyrazolo[3,4-d]-pyrimidines as highly potent inhibitors of the EGF-R tyrosine kinase. The most potent compounds 13, 14, 15, 17, 19, 22, 26, 28, and 30 of this series inhibited the EGF-R PTK with IC50 values below 10 nM. High selectivity toward a panel of nonreceptor tyrosine kinases (c-Src, upsilon-Abl) and serine/threonine kinases (PKC alpha, CDK1) was observed. In cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by compounds 13, 15, 19, 22, and 23 at IC50 values below 50 nM, whereas PDGF-induced tyrosine phosphorylation was not affected by concentrations up to 10 mu M, thus indicating high selectivity for the inhibition of the ligand-activated EGF-R signal transduction pathway. Compounds 15 and 19 inhibited proliferation of the EGF-dependent MK cell line with IC50 values below 0.5 mu M. In addition, two compounds, 9 and 11, showing satisfactory oral bioavailability in mice after oral administration, exhibited good in vivo efficacy at doses of 12.5 and 50 mg/kg in a nude mouse tumor model using xenografts of the EGF-R overexpressing A431 cell line. From SAR studies, a binding mode for 4-(phenylamino)-1H-pyrazolo[3,4-d]pyrimidines, especially for compound 15, at the ATP-binding site of the EGF-R tyrosine kinase is proposed. 4-(Phenylamino)-1H-pyrazolo[3,4-d]pyrimidines represent a new class of highly potent tyrosine kinase inhibitors which preferentially inhibit the EGF-mediated signal transduction pathway and have the potential for further evaluation as anticancer agents.

  DOI：

  10.1021/jm970124v
• 作为产物：
  描述：

  4-甲氧基苯二硫代甲酸甲酯 在 sodium hydride 作用下， 以 水 为溶剂， 反应 3.5h， 生成 2-[(4-Methoxyphenyl)-methylsulfanylmethylidene]propanedinitrile
  参考文献：
  名称：

  Tominaga, Yoshinori; Matsuoka, Yoshiki; Oniyama, Yukio, Journal of Heterocyclic Chemistry, 1990, vol. 27, # 3, p. 647 - 660

  摘要：

  DOI：

文献信息

• Patzel; Ushmajev; Liebscher, Synthesis, 1993, # 5, p. 525 - 529
  作者：Patzel、Ushmajev、Liebscher

  DOI：——

  日期：——
• A Novel Preparation of Polarized Ethylenes by the Reaction of Thioamides or Dithiocarboxylates with Tetracyanoethylene Oxide. Synthesis of Pyrazoles and Pyrimides
  作者：Yoshinori Tominaga、Yoshiki Matsuoka、Shinya Kohra、Akira Hosomi

  DOI：10.3987/r-1987-03-0613

  日期：——
• TOMINAGA, YOSHINORI;MATSUOKA, YOSHIKI;ONIYAMA, YUKIO;UCHIMURA, YOSHIMITSU+, J. HETEROCYCL. CHEM., 27,(1990) N, C. 647-660
  作者：TOMINAGA, YOSHINORI、MATSUOKA, YOSHIKI、ONIYAMA, YUKIO、UCHIMURA, YOSHIMITSU+

  DOI：——

  日期：——
• TOMINAGA, YOSHINORI;MATSUOKA, YOSHIKI;KOHRA, SHINYA;HOSOMI, AKIRA, HETEROCYCLES, 26,(1987) N 3, 613-616
  作者：TOMINAGA, YOSHINORI、MATSUOKA, YOSHIKI、KOHRA, SHINYA、HOSOMI, AKIRA

  DOI：——

  日期：——
• Use of a Pharmacophore Model for the Design of EGF-R Tyrosine Kinase Inhibitors:  4-(Phenylamino)pyrazolo[3,4-<i>d</i>]pyrimidines
  作者：Peter Traxler、Guido Bold、Joerg Frei、Marc Lang、Nicholas Lydon、Helmut Mett、Elisabeth Buchdunger、Thomas Meyer、Marcel Mueller、Pascal Furet

  DOI：10.1021/jm970124v

  日期：1997.10.1

  In the course of the random screening of a pool of CIBA chemicals, the two pyrazolopyrimidines 1 and 2 have been identified as fairly potent inhibitors of the EGF-R tyrosine kinase. Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGF-R protein tyrosine kinase (PTK), the class of the pyrazolo[3,4-d]pyrimidines was then optimized in an interactive process leading to a series of 4-(phenylamino)-1H-pyrazolo[3,4-d]-pyrimidines as highly potent inhibitors of the EGF-R tyrosine kinase. The most potent compounds 13, 14, 15, 17, 19, 22, 26, 28, and 30 of this series inhibited the EGF-R PTK with IC50 values below 10 nM. High selectivity toward a panel of nonreceptor tyrosine kinases (c-Src, upsilon-Abl) and serine/threonine kinases (PKC alpha, CDK1) was observed. In cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by compounds 13, 15, 19, 22, and 23 at IC50 values below 50 nM, whereas PDGF-induced tyrosine phosphorylation was not affected by concentrations up to 10 mu M, thus indicating high selectivity for the inhibition of the ligand-activated EGF-R signal transduction pathway. Compounds 15 and 19 inhibited proliferation of the EGF-dependent MK cell line with IC50 values below 0.5 mu M. In addition, two compounds, 9 and 11, showing satisfactory oral bioavailability in mice after oral administration, exhibited good in vivo efficacy at doses of 12.5 and 50 mg/kg in a nude mouse tumor model using xenografts of the EGF-R overexpressing A431 cell line. From SAR studies, a binding mode for 4-(phenylamino)-1H-pyrazolo[3,4-d]pyrimidines, especially for compound 15, at the ATP-binding site of the EGF-R tyrosine kinase is proposed. 4-(Phenylamino)-1H-pyrazolo[3,4-d]pyrimidines represent a new class of highly potent tyrosine kinase inhibitors which preferentially inhibit the EGF-mediated signal transduction pathway and have the potential for further evaluation as anticancer agents.