(S,E)-N-(2-chlorobenzylidene)-2-methylpropane-2-sulfinamide | 1402598-94-0

• 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: (S,E)-N-(2-chlorobenzylidene)-2-methylpropane-2-sulfinamide
• 英文别名: (NE,S)-N-[(2-chlorophenyl)methylidene]-2-methylpropane-2-sulfinamide
• CAS: 1402598-94-0
• 化学式: C₁₁H₁₄ClNOS
• 分子量: 243.757
• InChiKey: ZRAYQPCAUZXCPZ-NRUITVPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S,E)-N-(2-chlorobenzylidene)-2-methylpropane-2-sulfinamide 在 盐酸 、 4-二甲氨基吡啶 、 正丁基锂 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 N-((R)-(2-chlorophenyl)(7-(4-((1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyridinyl)-1-benzothiophen-2-yl)methyl)-3,4-dihydro-2H-1,5-benzodioxepine-7-sulfonamide
  参考文献：
  名称：

  [EN] BENZODIOXEPINE AND BENZODIOXINE COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN FOR THE TREATMENT OF DIABETES
  [FR] BENZODIOXÉPINE ET COMPOSÉS DE BENZODIOXINE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE POUR LE TRAITEMENT DU DIABÈTE

  摘要：

  本发明涉及与葡萄糖激酶调节蛋白相互作用的式I或II的化合物，或其药学上可接受的盐。此外，本发明涉及使用这些化合物或其药学上可接受的盐治疗2型糖尿病和其他涉及葡萄糖激酶调节蛋白的疾病和/或症状的方法，以及含有这些化合物或其药学上可接受的盐的药物组合物。

  公开号：

  WO2012138776A1
• 作为产物：
  描述：

  2-氯苯甲醛 、 S-叔丁基亚磺酰胺 在 magnesium sulfate 、 copper(II) sulfate 作用下， 以 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 为溶剂， 以89%的产率得到(S,E)-N-(2-chlorobenzylidene)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents

  摘要：

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.

  DOI：

  10.1021/jm501740a

文献信息

• KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
  申请人：Pauls Heinz W.

  公开号：US20140005167A1

  公开（公告）日：2014-01-02

  The present teachings provide a compound represented by structural formula (I): or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof.

  本教学提供了一种由结构式(I)表示的化合物，或其药用可接受的盐。还描述了药物组合物及其使用方法。
• [EN] INDAZOLE COMPOUNDS AS KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME<br/>[FR] COMPOSÉS INDAZOLE UTILISÉS COMME INHIBITEURS DE KINASE ET MÉTHODE DE TRAITEMENT DU CANCER AVEC LESDITS COMPOSÉS
  申请人：UNIV HEALTH NETWORK

  公开号：WO2013053051A1

  公开（公告）日：2013-04-18

  The present teaching provide indazole compounds represented by Structural Formulae (I) or (I') or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as TTK protein kinase, polo-like kinase 4 (PLK4) and Aurora kinases having anticancer activity against breast cancer cells, colon cancer cells, and ovarian cancer cells.

  本教学提供了由结构式（I）或（I'）表示的吲唑化合物或其药用可接受的盐。还描述了这些药物组合物及其用作蛋白激酶抑制剂的方法，如对乳腺癌细胞、结肠癌细胞和卵巢癌细胞具有抗癌活性的TTK蛋白激酶、极化样激酶4（PLK4）和极化激酶。
• [EN] KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME<br/>[FR] INHIBITEURS DE KINASE ET MÉTHODE DE TRAITEMENT DU CANCER À L'AIDE DE CEUX-CI
  申请人：UNIV HEALTH NETWORK

  公开号：WO2014056083A1

  公开（公告）日：2014-04-17

  The invention is a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. Values for the variables are provided herein. Also included is a pharmaceutical composition comprising the compound represented by Structural Formula (I) and a pharmaceutically acceptable carrier or diluent and methods of treating a subject with cancer with the compound of Structural Formula (I).

  该发明是由结构式（I）表示的化合物或其药学上可接受的盐。这里提供了变量的值。还包括一种含有由结构式（I）表示的化合物和药学上可接受的载体或稀释剂的药物组合物，以及使用结构式（I）的化合物治疗癌症患者的方法。
• [EN] BENZOTHIOPHENE SULFONAMIDES AND OTHER COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] BENZOTHIOPHÈNE SULFONAMIDES ET AUTRES COMPOSÉS QUI INTERAGISSENT AVEC UNE PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
  申请人：AMGEN INC

  公开号：WO2013173382A1

  公开（公告）日：2013-11-21

  The present invention relates to benzothiophene sulfonamides and other compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.

  本发明涉及苯并噻吩磺胺类化合物以及与葡萄糖激酶调控蛋白相互作用的其他化合物。此外，本发明涉及使用这些化合物或其药学上可接受的盐治疗2型糖尿病和其他涉及葡萄糖激酶调控蛋白的疾病和/或症状的方法，以及含有这些化合物或其药学上可接受的盐的药物组合物。
• INDAZOLE COMPOUNDS AS KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
  申请人：University Health Network

  公开号：US20140371202A1

  公开（公告）日：2014-12-18

  The present teaching provide indazole compounds represented by Structural Formulae (I) or (I′) or a pharmaceutically acceptable salt thereof. Also described are pharmaceutical compositions and methods of use thereof as protein kinase inhibitors, such as TTK protein kinase, polo-like kinase 4 (PLK4) and Aurora kinases having anticancer activity against breast cancer cells, colon cancer cells, and ovarian cancer cells.

  本教学提供由结构式（I）或（I'）所代表的吲唑化合物或其药学上可接受的盐。还描述了制备药物组合物和使用方法，作为蛋白激酶抑制剂，例如TTK蛋白激酶，极化样激酶4（PLK4）和极化激酶，对乳腺癌细胞，结肠癌细胞和卵巢癌细胞具有抗癌活性。