2-氯-N-甲基-3-吲哚醛肟 | 54778-21-1

• 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
• 中文名称: 2-氯-N-甲基-3-吲哚醛肟
• 中文别名: 2-氯-1-甲基-1H-吲哚-3-羧酸
• 英文名称: 2-chloro-1-methyl-1H-indole-3-carboxylic acid
• 英文别名: 1-methyl-2-chloroindole-3-carboxylic acid；2-chloro-1-methylindole-3-carboxylic acid；2-chloro-1-methyl-indole-3-carboxylic acid；2-Chlor-1-methylindol-3-carbonsaeure；1H-Indole-3-carboxylic acid, 2-chloro-1-methyl-
• CAS: 54778-21-1
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: AQPMLAXHNBHLTF-UHFFFAOYSA-N

物化性质

• 熔点：
  218 °C (decomp)
• 沸点：
  407.7±25.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氯-N-甲基-3-吲哚醛肟 在 氯化亚砜 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 2-chloro-1-methyl-1H-indole-3-carbonyl chloride
  参考文献：
  名称：

  酪氨酸激酶抑制剂。图6.N-和3-取代的2，2'-二硒代双（1H-吲哚）之间的结构-活性关系，用于抑制蛋白酪氨酸激酶，并比较了针对所选硫同类物的体内和体外研究。

  摘要：

  合成了少量的2,2'-二硒代双（1H-吲哚）系列，作为我们先前报道的2,2'-二硫代双（1H-吲哚）系列的氧化还原修饰同类物。利用类似于先前为二硫系列开发的化学方法，由2-卤代-3-吲哚羧酸前体制备化合物，所述前体在吲哚核的C-3位带有各种极性官能团，在N-1位带有小的烷基取代基。通过二氯二硒作为二硒的亲电子来源的新应用，从（R）-或（S）-色氨酸衍生出其他化合物，并开发了一种大大改进的制备2,2'-二硫代双（1H-吲哚）同源物的方法利用二氯化硫作为二硫化硫的来源。针对离体表皮生长因子受体（EGFr），血小板源性生长因子受体（PDGFr）和v-src酪氨酸激酶，该系列化合物显示出广泛的抑制活性，对EGFr的IC50 = 0.9至> 100 microM，对PDGFr的IC50 = 3.4至> 50 microM，对v-src为0.4-6.7 microM。通常，色氨酸衍生的化合物对EGFr

  DOI：

  10.1021/jm960689b
• 作为产物：
  描述：

  2-氯-1H-吲哚-3-甲醛 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 反应 22.5h， 生成 2-氯-N-甲基-3-吲哚醛肟
  参考文献：
  名称：

  酪氨酸激酶抑制剂。图6.N-和3-取代的2，2'-二硒代双（1H-吲哚）之间的结构-活性关系，用于抑制蛋白酪氨酸激酶，并比较了针对所选硫同类物的体内和体外研究。

  摘要：

  合成了少量的2,2'-二硒代双（1H-吲哚）系列，作为我们先前报道的2,2'-二硫代双（1H-吲哚）系列的氧化还原修饰同类物。利用类似于先前为二硫系列开发的化学方法，由2-卤代-3-吲哚羧酸前体制备化合物，所述前体在吲哚核的C-3位带有各种极性官能团，在N-1位带有小的烷基取代基。通过二氯二硒作为二硒的亲电子来源的新应用，从（R）-或（S）-色氨酸衍生出其他化合物，并开发了一种大大改进的制备2,2'-二硫代双（1H-吲哚）同源物的方法利用二氯化硫作为二硫化硫的来源。针对离体表皮生长因子受体（EGFr），血小板源性生长因子受体（PDGFr）和v-src酪氨酸激酶，该系列化合物显示出广泛的抑制活性，对EGFr的IC50 = 0.9至> 100 microM，对PDGFr的IC50 = 3.4至> 50 microM，对v-src为0.4-6.7 microM。通常，色氨酸衍生的化合物对EGFr

  DOI：

  10.1021/jm960689b

文献信息

• A new approach to the synthesis of rare thiazino[6,5-b]indol-4-one derivatives. First total synthesis of the indole phytoalexin cyclobrassinon
  作者：Peter Kutschy、Mojmı́r Suchý、Aldo Andreani、Milan Dzurilla、Vladimı́r Kováčik、Juraj Alföldi、Maddalena Rossi、Mária Gramatová

  DOI：10.1016/s0040-4020(02)01124-9

  日期：2002.10

  The first synthesis of the indole phytoalexin cyclobrassinon and some of its analogues, possessing a thiazino[6,5-b]indol-4-one tricyclic ring system was performed starting from 1-substitued 2-chloroindole-3-carboxaldehydes. The route employed the intramolecular Et3N-mediated or photochemical nucleophilic substitution of a chlorine atom in the 2-position of the indole ring with a sulfur atom as a key

  带有噻嗪[6,5 - b ]吲哚-4-酮三环系统的吲哚植物抗毒素环布拉索农及其某些类似物的首次合成从1-取代的2-氯吲哚-3-甲醛开始进行。该路线采用在分子内由Et 3 N介导或光化学的亲核取代吲哚环的2-位上的氯原子被硫原子作为关键步骤。对选定的肿瘤细胞系，细菌和真菌的生物学活性检查显示合成的化合物没有表达活性。
• 2-thioindoles (selenoindoles) and related disulfides (selenides) which
  申请人：Warner-Lambert

  公开号：US05464861A1

  公开（公告）日：1995-11-07

  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.

  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。
• A new photocyclization approach to the rare 1,3-thiazino[6,5-b]indol-4-one derivatives
  作者：Peter Kutschy、Mojmı́r Suchý、Aldo Andreani、Milan Dzurilla、Maddalena Rossi

  DOI：10.1016/s0040-4039(01)02040-8

  日期：2001.12

  The analogs of indole phytoalexin cyclobrassinon have been prepared in four steps from corresponding I-substituted 2-chloroindole-3-carboxylic acids, employing a hitherto unknown photochemical cyclization of new indolyl thiocarbamates to 1,3-thiazino[6,5-b]indole-4-one derivatives as a key step. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 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.
• Andreani, Aldo; Rambaldi, Mirella, Journal of Heterocyclic Chemistry, 1988, vol. 25, p. 1519 - 1523
  作者：Andreani, Aldo、Rambaldi, Mirella

  DOI：——

  日期：——