6-chloro-1-methyl-2-indolinethione | 156136-70-8

• 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: 6-chloro-1-methyl-2-indolinethione
• 英文别名: 6-chloro-1-methyl-2,3-dihydro-1H-indole-2-thione；6-chloro-1-methyl-3H-indole-2-thione
• CAS: 156136-70-8
• 化学式: C₉H₈ClNS
• mdl: MFCD19381939
• 分子量: 197.688
• InChiKey: JEXOQFIGJMQONR-UHFFFAOYSA-N

物化性质

• 沸点：
  294.2±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-chloro-1-methyl-2-indolinethione 在 air 、 sodium hydride 作用下， 以 甲醇 为溶剂， 生成 dithiobis(1H-indole-3-carboxamide) deriv. 10p
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared 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. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016
• 作为产物：
  描述：

  6-chloroisatin 3-hydrazone 在 sodium hydroxide 、 tetraphosphorus decasulfide 、 sodium 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 6-chloro-1-methyl-2-indolinethione
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared 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. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016

文献信息

• Enantioselective synthesis of indolo[2,3-b]-dihydrothiopyranones via [3+3] cycloaddition of chiral α,β-unsaturated acylammonium salts
  作者：Jing-Hai Jin、Xiang-Yu Li、Xiaoyan Luo、Wei-Ping Deng

  DOI：10.1016/j.tet.2018.09.024

  日期：2018.11

  nucleophile-catalyzed Michael addition/proton transfer/lactonization (NCMPL) organocascade process of chiral α,β-unsaturated acylammonium salts and indoline-2-thiones is described, which delivers the indolo[2,3-b]dihydrothiopyranone motifs in high yields (up to 97%) with good to excellent enantioselectivities (up to 98% ee).

  描述了亲核催化剂催化的手性α，β-不饱和酰基铵盐和二氢吲哚-2-硫酮的迈克尔加成/质子转移/内酯化（NCMPL）有机级联反应，该反应可高产率地产生吲哚[2,3- b ]二氢噻喃酮基序（高达97％）具有良好至优异的对映选择性（高达98％ee）。
• Copper-catalyzed synthesis of 2-sulfenylindoles from indoline-2-thiones and aryl iodides
  作者：Shiping Zhou、Genhua Xiao、Yun Liang

  DOI：10.1016/j.tetlet.2016.12.028

  日期：2017.1

  A novel and efficient method for synthesis of 2-sulfenylindole via copper-catalyzed coupling reaction of indoline-2-thiones with aryl iodides has been developed. A series of N-substituted and N-free 2-sulfenylindole were obtained in high yields. Furthermore, the method was employed to synthesis of benzothieno[2,3-b]indoles from indoline-2-thiones with 1,2-diiodobenzene in the presence of CuI and Pd(OAc)2

  通过铜催化的吲哚-2-硫酮与芳基碘的偶联反应合成2-亚磺酰基吲哚的新方法已经得到了发展。以高收率获得了一系列的N-取代的和不含N的2-亚磺酰基吲哚。此外，该方法用于在CuI和Pd（OAc）2作为催化剂存在下，由吲哚啉-2-硫酮与1,2-二碘代苯合成苯并噻吩并[2,3- b ]吲哚。
• 一种手性吲哚并噻喃化合物的合成方法
  申请人：苏州大学

  公开号：CN104497007B

  公开（公告）日：2017-01-18

  本发明公开了一种手性吲哚并噻喃类化合物的合成方法，具体为以硫代吲哚酮与苯甲醛丙二腈为反应物，在手性多功能1R,2R‑二苯基乙二胺硫脲催化剂催化下，在溶剂中合成得到产物。本发明公开的方法原料简单易得，反应条件温和，后处理简单方便，适用的底物范围广，收率高，对映选择性高；由此合成得到的产物可用以合成药物和杀虫剂的中间体。
• Stereocontrolled Construction of the 3,4-Dihydrothiacarbazol-2(9<i>H</i>)-one Skeleton by Using Bifunctional Squaramide-Catalyzed Cascade Reactions
  作者：Shanren Chen、Jianping Pan、Youming Wang、Zhenghong Zhou

  DOI：10.1002/ejoc.201403078

  日期：2014.12

  approach for the stereocontrolled construction of the 3,4-dihydrothiacarbazol-2(9H)-one skeleton has been developed. In the presence of a bifunctional squaramide catalyst that was derived from L-tert-leucine, the asymmetric tandem Michael/thiolysis reactions of 9-methylindoline-2-thiones and N-alkynoylphthalimides proceeded efficiently to furnish the desired 3,4-dihydrothiacarbazol-2(9H)-one derivatives

  3,4-dihydrothiacarbazol-2(9H)-one 骨架立体控制结构的有效方法已经开发出来。在衍生自 L-叔亮氨酸的双功能方酸酰胺催化剂存在下，9-甲基二氢吲哚-2-硫酮和 N-炔基邻苯二甲酰亚胺的不对称串联迈克尔/硫解反应有效地提供了所需的 3,4-二氢噻咔唑-2 (9H)-一种衍生物，收率令人满意，对映选择性高（高达 98% ee）。
• Asymmetric Construction of Spiro[thiopyranoindole-benzoisothiazole] Scaffold via a Formal [3 + 3] Spiroannulation
  作者：Xiang Chen、Jun-Qi Zhang、Shao-Jie Yin、Hai-Yan Li、Wei-Qun Zhou、Xing-Wang Wang

  DOI：10.1021/acs.orglett.5b01951

  日期：2015.9.4

  An enantioselective formal thio[3 + 3] spiroannulation reaction of indoline-2-thiones to 1-azadienes has been developed by the use of a quinine-derived bifunctional tertiary amine-thiourea catalyst, which furnished a series of optically active spiro[thiopyranoindole-benzoisothiazole] heterocycles with a spiro quaternary C–N/C–S stereogenic centers in high yields with good to excellent diastereo- and

  通过使用奎宁衍生的双官能叔胺-硫脲催化剂开发了吲哚啉-2-硫酮与1-氮杂二烯的对映体选择性硫[3 + 3]螺环化反应，该催化剂提供了一系列旋光性螺[thiopyranoindole-具有螺环季铵化C–N / C–S立体异构中心的苯并异噻唑]杂环化合物，其高收率具有出色的非对映选择性和对映选择性。