6-chloro-1-methylindolin-2-one | 156136-55-9

• 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-methylindolin-2-one
• 英文别名: 6-chloro-1-methyl-3H-indol-2-one
• CAS: 156136-55-9
• 化学式: C₉H₈ClNO
• 分子量: 181.622
• InChiKey: SIBHQHVZRLURMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-chloro-1-methylindolin-2-one 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 以87%的产率得到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
• 作为产物：
  描述：

  6-chloroisatin 3-hydrazone 在 sodium hydroxide 、 sodium 作用下， 以 乙醇 、 水 为溶剂， 生成 6-chloro-1-methylindolin-2-one
  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

• 1H-Pyrimido[4,5-b]indole derivatives, their preparation and therapeutic use
  申请人：Froissant Jacques

  公开号：US20080125410A1

  公开（公告）日：2008-05-29

  The invention concerns compounds of general formula (I): Wherein n, X, Y, R 1 and R 2 are as defined herein. The invention also concerns a method for preparing the compounds and their therapeutic use.

  这项发明涉及一般式(I)的化合物： 其中n、X、Y、R1和R2如本文所定义。该发明还涉及制备这些化合物以及它们的治疗用途的方法。
• BENZYLIDENE-INDOLINONE COMPOUNDS AND THEIR MEDICAL USE
  申请人：GO Mei Lin

  公开号：US20130035364A1

  公开（公告）日：2013-02-07

  Compounds of general formula I: wherein R 1a , R 1b , R 2 , R 3a , R 3b and X are as defined herein are tyrosine kinase inhibitors and are useful for the treatment of various diseases and conditions, for example cancer.

  通式I的化合物： 其中 R 1a ，R 1b ，R 2 ，R 3a ，R 3b 和X如本文所定义的那样是酪氨酸激酶抑制剂，对于治疗各种疾病和病况，例如癌症，是有用的。
• Highly Enantioselective Michael Addition of 2-Oxindole- 3-carboxylate Esters to Nitroolefins Promoted by Cinchona Alkaloid-Thiourea-Brønsted Acid Cocatalysts
  作者：Xianjie Chen、Wei Zhu、Wangke Qian、Enguang Feng、Yu Zhou、Jinfang Wang、Hualiang Jiang、Zhu-Jun Yao、Hong Liu

  DOI：10.1002/adsc.201200206

  日期：2012.8.13

  A highly efficient organocatalyzed Michael addition of 2-oxindole-3-carboxylate esters to nitroolefins using a Cinchona alkaloid-thiourea and an achiral Brønsted acid as cooperative organocatalysts is reproted that affords significantly improved enantioselectivity and diastereoselectivity. It also provides an efficient approach to the synthesis of spirooxindole derivatives with high enantioselectivity

  使用金鸡纳生物碱-硫脲和非手性布朗斯台德酸作为协同有机催化剂，可以高效地将2-氧吲哚-3-羧酸酯的迈克尔加成到硝基烯烃上，从而大大提高了对映选择性和非对映选择性。它还为合成具有高对映选择性的螺并恶吲哚衍生物提供了一种有效的方法。
• Hydrogen-Bond-Directed Formal [5 + 1] Annulations of Oxindoles with Ester-Linked Bisenones: Facile Access to Chiral Spirooxindole δ-Lactones
  作者：Shuai Zhao、Jun-Bing Lin、Yuan-Yuan Zhao、Yong-Min Liang、Peng-Fei Xu

  DOI：10.1021/ol500547e

  日期：2014.3.21

  A novel bifunctional thiourea catalyzed formal [5 + 1] cycloaddition of oxindoles and ester-linked bisenones was successfully developed. This strategy involves two sequential Michael additions, leading to spirooxindole δ-lactones with three contiguous stereocenters including an all-carbon quaternary center with high diastereo- and enantioselectivites. In addition, a remarkable N-substituent effect

  一种新型的双功能硫脲催化了羟吲哚和酯连接的双硒酮的正式[5 +1]环加成反应。该策略涉及两个连续的迈克尔加成，从而产生具有三个连续立体中心的螺环吲哚δ-内酯，包括具有高非对映体和对映体选择性的全碳四元中心。另外，在反应性和选择性上观察到了显着的N-取代作用。
• Asymmetric Synthesis of α-Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis
  作者：Sushovan Paladhi、Sang Yeon Park、Jung Woon Yang、Choong Eui Song

  DOI：10.1021/acs.orglett.7b02628

  日期：2017.10.6

  Biologically relevant chiral 3,3-disubstituted oxindole products containing a β-fluoroamine unit are obtained in high yields and with excellent stereoselectivity (up to 99% ee, dr >20:1 for syn) through the organocatalytic direct Mannich reaction of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones as the bench-stable precursors of sensitive imines by using a chiral oligoethylene glycol

  通过3-氟的有机催化直接曼尼希反应，可以高收率且具有出色的立体选择性（高达99％ee，syn的dr> 20：1 ），获得了具有β-氟胺单元的生物相关的手性3,3-二取代的羟吲哚产物。分别使用手性低聚乙二醇和KF作为阳离子结合催化剂和碱，将-oxindoles作为氟烯酸酯前体，将α-酰胺基砜作为敏感亚胺的替补稳定前体。该协议可以轻松扩展，而不会影响不对称感应。此外，该协议也已成功扩展到生成四取代的C–Cl和C–Br立体异构中心。