methyl (3Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetate | 916047-65-9

• 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: methyl (3Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetate
• 英文别名: methyl (2Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetate；methyl (2Z)-2-(5-chloro-2-oxo-1H-indol-3-ylidene)-2-cyanoacetate
• CAS: 916047-65-9
• 化学式: C₁₂H₇ClN₂O₃
• 分子量: 262.652
• InChiKey: CSDYYCJYUVNTNI-NTMALXAHSA-N

物化性质

• 沸点：
  478.8±45.0 °C(Predicted)
• 密度：
  1.473±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (3Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetate 、 硝基甲烷 在 哌啶 作用下， 反应 3.0h， 生成 methyl (5-chloro-3-(nitromethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)(cyano)acetate
  参考文献：
  名称：

  Discovery of a New Class of Potent, Selective, and Orally Bioavailable CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases

  摘要：

  A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound (5) was found during a high-throughput screening campaign. Structure - activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds (R)-58 and (R)-71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.

  DOI：

  10.1021/jm701383e
• 作为产物：
  描述：

  5-甲基靛红 、 氰乙酸甲酯 以71.429%的产率得到
  参考文献：
  名称：

  在离子液体中通过[3 + 2]环加成反应合成高度官能化的新型双螺双氧吲哚衍生物并进行立体化学研究

  摘要：

  的反应性模式ë / ž异构化（polaraziableÇ C键）烷基2-氰基-2-乙酸酯研究了产生的偶氮甲碱内鎓盐（2- oxoindolin -3-亚基）在原位从靛红和肌氨酸或脯氨酸立体化学产生的脱羧缩合通过[3 + 2]环加成反应产生多达四个立体异构中心的新型二螺双氧杂吲哚衍生物。为了研究与肌氨酸的偶氮甲叶立德的反应，2-氰基-2-（2-氧代吲哚-3-甲叉基）乙酸烷基酯的E异构体作为双极亲油性参与生产双螺并吡咯烷-双ox吲哚，而对于脯氨酸的偶氮甲ine基内鎓盐则为Z2-氰基-2-（2-氧代吲哚-3-亚烷基）乙酸烷基酯的异构体参与在[bmim] BF 4离子液体中作为单一产物生成双螺并吡咯烷二氮杂双酚类，作为环境友好的溶剂，无需使用任何催化剂即可获得优异的收率。良好的官能团耐受性和可用底物的广泛范围是具有高度化学，区域和立体选择性的本方法的其他突出特征。两种类型的环加合物的结构和相对立体化学均通过单晶X射线衍射以及1

  DOI：

  10.1016/j.tet.2012.12.021

文献信息

• Tricyclic spiro derivatives as CRTH2 modulators
  申请人：Schwarz Matthias

  公开号：US20090318486A1

  公开（公告）日：2009-12-24

  The present invention is related to the use of spiro derivatives of Formula (I) for the treatment and/or prevention of allergic diseases, inflammatory dermatoses and other diseases with an inflammatory component. Specifically, the present invention is related to the use of spiro derivatives for the modulation of CRTH2 activity.

  本发明涉及使用式(I)的螺环衍生物用于治疗和/或预防过敏性疾病、炎症性皮肤病和其他具有炎症成分的疾病。具体而言，本发明涉及使用螺环衍生物来调节CRTH2活性。
• WO2006/125784
  申请人：——

  公开号：——

  公开（公告）日：——
• TRICYCLIC SPIRO DERIVATIVES AS CRTH2 MODULATORS
  申请人：Merck Serono SA

  公开号：EP1891075B1

  公开（公告）日：2011-10-19
• US8236963B2
  申请人：——

  公开号：US8236963B2

  公开（公告）日：2012-08-07
• Discovery of a New Class of Potent, Selective, and Orally Bioavailable CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases
  作者：Stefano Crosignani、Patrick Page、Marc Missotten、Véronique Colovray、Christophe Cleva、Jean-François Arrighi、John Atherall、Jackie Macritchie、Thierry Martin、Yves Humbert、Marilène Gaudet、Doris Pupowicz、Maurizio Maio、Pierre-André Pittet、Lucia Golzio、Claudio Giachetti、Cynthia Rocha、Gérald Bernardinelli、Yaroslav Filinchuk、Alexander Scheer、Matthias K. Schwarz、André Chollet

  DOI：10.1021/jm701383e

  日期：2008.4.1

  A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound (5) was found during a high-throughput screening campaign. Structure - activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds (R)-58 and (R)-71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.