2,2'-dithiobis(N,1-dimethyl-1H-indole-3-carboxamide)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,2'-dithiobis(N,1-dimethyl-1H-indole-3-carboxamide)
• 英文别名: dithiobis(1H-indoles) deriv. 3；N,1-dimethyl-2-[[1-methyl-3-(methylcarbamoyl)indol-2-yl]disulfanyl]indole-3-carboxamide
• 化学式: C₂₂H₂₂N₄O₂S₂
• 分子量: 438.574
• InChiKey: XUXNEGDCCYQQNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2'-dithiobis(N,1-dimethyl-1H-indole-3-carboxamide) 生成 2-[[3-(dimethylcarbamoyl)-1-methylindol-2-yl]disulfanyl]-N,N,1-trimethylindole-3-carboxamide
  参考文献：
  名称：

  Palmer Brian D., Rewcastle Gordon W., Thompson Andrew M., Boyd Maruta, Sh+, J. Med. Chem, 38 (1995) N 1, S 58-67

  摘要：

  DOI：
• 作为产物：
  描述：

  2-chloro-N,1-dimethyl-1H-indole-3-carboxamide 以70%的产率得到
  参考文献：
  名称：

  Palmer Brian D., Rewcastle Gordon W., Thompson Andrew M., Boyd Maruta, Sh+, J. Med. Chem, 38 (1995) N 1, S 58-67

  摘要：

  DOI：

文献信息

• Synthesis of C-5 benzoyl and azido functionalized 2,2′-dithiobis-and 2,2′-diselenobis(1<i>H</i>-indoles)
  作者：Li Sun、J. Ronald Rubin、Alan J. Kraker、H. D. Hollis Showalter

  DOI：10.1002/jhet.5570340505

  日期：1997.9

  Novel methods for the synthesis of C-5 benzoyl and azido analogues of 2,2′-dithiobis(1H-indole), 1, and 2,2′-diselenobis(1H-indole), 2, are described to further explore the structure activity relationships in this region of the molecule. Analogues 3-i displayed inhibitory activity (IC50 = 0.45-2.03 μ) toward the catalytic domain of the epidermal growth factor receptor tyrosine kinase that was equivalent

  为2,2'-二硫代双的C-5的苯甲酰基和叠氮基类似物的合成新方法（1 ħ -吲哚），1,2-和2,2'- diselenobis（1 ħ -吲哚），2，描述进一步探索在该分子区域中的结构活性关系。类似物3-i对表皮生长因子受体酪氨酸激酶的催化域表现出抑制活性（IC 50 = 0.45-2.03μ），其等效于或优于未取代的化合物1和2。Friedel-Crafts苯甲酰化的区域化学通过X-射线晶体学测定到1上。为了测试此类化合物通过以下途径与表皮生长因子受体酪氨酸激酶相互作用的潜力通过巯基交换机理，进行了2,2'-二硫代双（1 H-吲哚）与谷胱甘肽的反应，并对产物进行了表征。
• Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases
  作者：Brian D. Palmer、Gordon W. Rewcastle、Andrew M. Thompson、Maruta Boyd、H. D. Hollis Showalter、Anthony D. Sercel、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm00001a011

  日期：1995.1

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.
• Palmer Brian D., Rewcastle Gordon W., Thompson Andrew M., Boyd Maruta, Sh+, J. Med. Chem, 38 (1995) N 1, S 58-67
  作者：Palmer Brian D., Rewcastle Gordon W., Thompson Andrew M., Boyd Maruta, Sh+

  DOI：——

  日期：——