methyl 3-(4-chlorophenyl)-3-oxo-2-(triphenylphosphoranylidene)propanoate | 96277-02-0

• 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: methyl 3-(4-chlorophenyl)-3-oxo-2-(triphenylphosphoranylidene)propanoate
• 英文别名: Triphenylphosphin-<4-chlor-benzoyl>-methoxycarbonyl-methylen；(4-Chlorobenzoyl)(triphenylphosphoranylidene)acetic acid methyl ester；methyl 3-(4-chlorophenyl)-3-oxo-2-(triphenyl-λ5-phosphanylidene)propanoate
• CAS: 96277-02-0
• 化学式: C₂₈H₂₂ClO₃P
• 分子量: 472.908
• InChiKey: SODQRSIJSZXWSI-UHFFFAOYSA-N

物化性质

• 熔点：
  131-132 °C
• 沸点：
  617.0±57.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-chlorophenyl)-3-oxo-2-(triphenylphosphoranylidene)propanoate 生成 对氯苯丙炔酸
  参考文献：
  名称：

  Maerkl,G., Chemische Berichte, 1961, vol. 94, p. 3005 - 3010

  摘要：

  DOI：
• 作为产物：
  描述：

  4-氯苯甲酰氯 、 甲氧羰基亚甲基三苯基正膦 在 2,6-二甲基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 methyl 3-(4-chlorophenyl)-3-oxo-2-(triphenylphosphoranylidene)propanoate
  参考文献：
  名称：

  蛋白酪氨酸磷酸酶SHP2的选择性抑制剂在体外和体内阻断细胞运动和癌细胞的生长

  摘要：

  酪氨酸蛋白磷酸酶SHP2（src同源区域2域磷酸酶； PTPN11）的选择性抑制剂是通过化学合成和基于结构的合理设计相结合而产生的，该酶在许多人类肿瘤中均被解除调节。制备了70种吡啶并唑-4-亚甲基肼基苯磺酸盐，并在酶分析中进行了评估。使用新生成的SHP2晶体结构在计算机上模拟了活性抑制剂的结合模式。最强大的化合物GS‐493（4 ‐ {（2 Z）‐2‐ [1、3‐双（4‐硝基苯基）‐5‐oxo‐1,5‐二氢‐4 H‐吡唑‐4‐liden]]肼基苯磺酸；25）抑制SHP2，IC 50值为71±15 n M在酶检测中，对SHP2的活性比对相关SHP1和PTP1B的活性高29到45倍。在细胞培养实验中，发现化合物25可以阻断肝细胞生长因子（HGF）刺激的人胰腺癌（HPAF）细胞的上皮-间质转化，这通过最小最小细胞距离的减少来表明。此外，在软琼脂中，有25种抑制了非小细胞肺癌LXFA 526L细

  DOI：

  10.1002/cmdc.201500015

文献信息

• Palladium-Catalyzed Ylidyl-Carbonylation of Aryl Halides To Produce α-Acylphosphoranes
  作者：Xiaojun Guo、Wei Ma、Dong Xue、Chao Wang、Jianliang Xiao

  DOI：10.1021/acs.orglett.6b02278

  日期：2016.10.7

  An efficient synthesis of α-acylphosphoranes by palladium-catalyzed carbonylation of aryl iodides with carbon monoxide and stabilized phosphonium ylides has been developed. Featuring 44 examples, the protocol displayed a wide substrate scope under mild reaction conditions, showcasing its potential in synthetic organic chemistry.

  已经开发了通过钯催化一氧化碳和稳定化的碘化ides的钯催化的芳基碘的羰基化反应，可以高效合成α-酰基phosph。该方案包含44个实例，在温和的反应条件下显示了广泛的底物范围，显示了其在合成有机化学中的潜力。
• Shp-2 Inhibitors, Pharmaceutical Compositons Comprising Them and Their Use For Treating Phosphatase-Mediated Diseases
  申请人：Hellmuth Klaus

  公开号：US20080194563A1

  公开（公告）日：2008-08-14

  The present invention relates to small molecule protein tyrosine phosphatase inhibitors, especially Shp-2 inhibitors, of formula (I) and/or (II), and to pharmaceutical compositions comprising them. The invention is also directed to the use of said compounds for the treatment of phosphatase-mediated diseases, especially cancer and metastasis. The invention further concerns a method for treating a proliferative disease, a genetic disorder, an autoimmune disease, an angiogenic disorder or cancer in a patient in need of such treatment, comprising administering to said patient a therapeutically effective amount of at least one compound of formula (I) and/or (II).

  本发明涉及小分子蛋白酪氨酸磷酸酶抑制剂，特别是Shp-2抑制剂，其化学式为(I)和/或(II)，以及包含它们的制药组合物。该发明还涉及使用所述化合物治疗磷酸酶介导的疾病，特别是癌症和转移。本发明还涉及一种治疗增殖性疾病、遗传性疾病、自身免疫性疾病、血管生成障碍或癌症的方法，包括向该患者施用至少一种化合物(I)和/或(II)的治疗有效量。
• Maerkl,G., Chemische Berichte, 1961, vol. 94, p. 3005 - 3010
  作者：Maerkl,G.

  DOI：——

  日期：——
• Pyranone, Thiopyranone, and Pyridone Inhibitors of Phosphatidylinositol 3-Kinase Related Kinases. Structure−Activity Relationships for DNA-Dependent Protein Kinase Inhibition, and Identification of the First Potent and Selective Inhibitor of the Ataxia Telangiectasia Mutated Kinase
  作者：Jonathan J. Hollick、Laurent J. M. Rigoreau、Celine Cano-Soumillac、Xiaoling Cockcroft、Nicola J. Curtin、Mark Frigerio、Bernard T. Golding、Sophie Guiard、Ian R. Hardcastle、Ian Hickson、Marc G. Hummersone、Keith A. Menear、Niall M. B. Martin、Ian Matthews、David R. Newell、Rachel Ord、Caroline J. Richardson、Graeme C. M. Smith、Roger J. Griffin

  DOI：10.1021/jm061121y

  日期：2007.4.1

  Structure-activity relationships have been investigated for inhibition of DNA-dependent protein kinase (DNA-PK) and ATM kinase by a series of pyran-2-ones, pyran-4-ones, thiopyran-4-ones, and pyridin-4-ones. A wide range of IC50 values were observed for pyranones and thiopyranones substituted at the 6-position, with the 3- and 5-positions proving intolerant to substitution. Related pyran-2-ones, pyran-4-ones, and thiopyran-4-ones showed similar IC50 values against DNA-PK, whereas the pyridin-4-one system proved, in general, ineffective at inhibiting DNA-PK. Extended libraries exploring the 6-position of 2-morpholino-pyran-4-ones and 2-morpholino-thiopyrano-4-ones identified the first highly potent and selective ATM inhibitor 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (151C; ATM; IC50 = 13 nM) and revealed constrained SARs for ATM inhibition compared with DNA-PK. One of the most potent DNA-PK inhibitors identified, 2-(4-methoxyphenyl)-6-(morpholin-4-yl)pyran-4-one (16; DNA-PK; IC50 = 220 nM) effectively sensitized HeLa cells to the topoisomerase II inhibitor etoposide in vitro.
• A New Synthesis of α-Acylphosphorane
  作者：Li Wang、Xian Huang

  DOI：10.1080/00397919408012647

  日期：1994.3