N-methyl-N-phenyl 2-chloro-1-methylindole-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-methyl-N-phenyl 2-chloro-1-methylindole-3-carboxamide
• 英文别名: 2-chloro-N,1-dimethyl-N-phenylindole-3-carboxamide
• 化学式: C₁₇H₁₅ClN₂O
• 分子量: 298.772
• InChiKey: GPVCYHMLRDOOPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  25.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-methyl-N-phenyl 2-chloro-1-methylindole-3-carboxamide 在 sodium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 19.0h， 以85%的产率得到5,11-dihydro-5,11-dimethyl-6H-indolo[3,2-c]quinolin-6-one
  参考文献：
  名称：

  N-芳基邻氯杂芳烃甲酰胺的光环化合成吡唑并[4,3-c]喹啉-4-酮和吲哚[3,2-c]喹啉-6-酮

  摘要：

  5-氯-N-苯基-1 H-吡唑光环化高效合成吡唑并[4,3-C]喹啉-4-酮和吲哚[3,2-C]喹啉-6-酮丙酮中的 -4-羧酰胺和 2-氯-N-苯基-1 H-吲哚-3-羧酰胺。

  DOI：

  10.1055/s-2008-1067013
• 作为产物：
  描述：

  2-氯-N-甲基-3-吲哚醛肟 、 N-甲基苯胺 在 氯化亚砜 作用下， 以67%的产率得到N-methyl-N-phenyl 2-chloro-1-methylindole-3-carboxamide
  参考文献：
  名称：

  2-thioindoles (selenoindoles) and related disulfides (selenides) which

  摘要：

  本文揭示了2-硫代吲哚（2-硒代吲哚）及类似的2-吲哚硫酮（2-吲哚硒酮）和聚硫化物（硒化物）化合物，以及其盐、生产方法、生产中间体、含有该类化合物的药物组合物，以及使用这些组合物来抑制蛋白激酶依赖性疾病或治疗哺乳动物中的异常细胞生长的方法。

  公开号：

  US05464861A1

文献信息

• 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.
• 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0654024A1

  公开（公告）日：1995-05-24
• US5464861A
  申请人：——

  公开号：US5464861A

  公开（公告）日：1995-11-07
• US5556874A
  申请人：——

  公开号：US5556874A

  公开（公告）日：1996-09-17
• [EN] 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES<br/>[FR] 2-THIOINDOLES (SELENOINDOLES) ET DISULFURES ASSOCIES (SELENIURES) INHIBANT LES TYROSINE KINASES ET PRESENTANT DES PROPRIETES ANTITUMORALES
  申请人：——

  公开号：WO1994003427A1

  公开（公告）日：1994-02-17

  [EN] 2-Thioindoles (2-selenoindoles) and analogous 2-indolinethione (2-indolineselenone) and polysulfide (selenide) compounds, salts thereof, methods of production, intermediates in their production, pharmaceutical compositions containing said compounds, and methods for inhibiting protein kinase dependent disease in a mammal or treating aberrant cell growth in a mammal, using said compositions, are disclosed.
  [FR] L'invention concerne des composés de 2-thioindoles (2-sélénoindoles) ainsi que de 2-indolinethione (2-indolinesélénone) et de polysulfure (séléniure) analogues, des sels de ceux-ci, des procédés de production, leurs intermédiaires de production, des compositions pharmaceutiques contenant lesdits composés, ainsi que des procédés d'inhibition de maladies liées à la kinase chez un mammifère, ou de traitement d'une croissance cellulaire aberrante chez un mammifère, à l'aide desdites compositions.