(4-(1-ethoxyvinyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone | 1016544-79-8

• 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: (4-(1-ethoxyvinyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: [4-(1-ethoxyethenyl)-2-(1,2,4-triazol-1-yl)phenyl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1016544-79-8
• 化学式: C₂₂H₂₃N₃O₅
• 分子量: 409.442
• InChiKey: OMLLVIVEKGDEMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  84.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4-(1-ethoxyvinyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 1-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)-2-bromoethanone
  参考文献：
  名称：

  BENZOPHENONE DERIVATIVES USEFUL FOR INHIBITING FORMATION OF MICROTUBULE

  摘要：

  本文披露了一种由式I表示的新型苯甲酮衍生物，其药学上可接受的盐，其水合物或溶剂合物，含有相同化合物的药理学组合物，以及将该组合物用作治疗药物。苯甲酮衍生物具有微管形成抑制活性，可用于通过杀死活跃增殖细胞来治疗恶性肿瘤的正常增殖状态。

  公开号：

  US20090275575A1
• 作为产物：
  描述：

  (4-bromo-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone 、 三丁基(1-乙氧基乙烯)锡 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以54.6%的产率得到(4-(1-ethoxyvinyl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Identification of CKD-516: A Potent Tubulin Polymerization Inhibitor with Marked Antitumor Activity against Murine and Human Solid Tumors

  摘要：

  Tubulin polymerization inhibitors had emerged as one of promising anticancer therapeutics because of their dual mechanism of action, i.e. apoptosis by cell-cycle arrest and VDA, vascular disrupting agent. VDAs are believed to be more efficient, less toxic, and several of them are currently undergoing clinical trials. To identify novel tubulin inhibitors that possess potent cytotoxicity and strong inhibition of tubulin polymerization as well as potent in vivo antitumor efficacy, we have utilized benzophenone scaffold. Complete SA R analysis of newly synthesized analogues that were prepared by incorporation of small heterocycles (C2, C4, and C5 position) into B-ring along with the evaluation of their in vitro cytotoxicity, tubulin polymerization inhibition, and in vivo antitumor activity allowed us to identify 22 (S516). Compound 22 was found to have potent cytotoxicity against several cancer cells including P-gp overexpressing MDR positive cell line (HCT15). It also induced cell cycle arrest at G(2)/M phase, which is associated with strong inhibition of tubulin polymerization. Its in vivo efficacy was improved by preparing its (L)-valine prodrug, 65 (CKD-516), which together with greatly improved aqueous solubility has shown marked antitumor efficacy against both murine tumors (CT26 and 3LL) and human xenogratfs (HCT116 and HCT15) in mice.

  DOI：

  10.1021/jm1002414

文献信息

• Benzophenone derivatives useful for inhibiting formation of microtubule
  申请人：Chong Kun Dang Pharmaceutical Corp.

  公开号：US08053439B2

  公开（公告）日：2011-11-08

  Disclosed herein are novel benzophenone derivatives represented by formula I, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, a pharmacological composition containing the same, and a use of the composition as therapeutic drugs. The benzophenone derivatives have an inhibition activity of microtubule formation and can be used to treat a normal proliferative state of a malignant tumor by killing the actively proliferating cells.

  本文揭示了一种新的苯甲酮衍生物，其化学式为I，其药学上可接受的盐，水合物或溶剂化物，含有该化合物的药理学组合物，以及将该组合物用作治疗药物的用途。苯甲酮衍生物具有微管形成抑制活性，可用于通过杀死活跃增殖的细胞治疗恶性肿瘤的正常增殖状态。
• WO2008/38955
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a potent tubulin polymerization inhibitor: Synthesis and evaluation of water-soluble prodrugs of benzophenone analog
  作者：Jaekwang Lee、Suyeal Bae、Seo-hee Lee、Hojin Choi、Young Hoon Kim、Soo Jin Kim、Gyu Tae Park、Seung Kee Moon、Dal-Hyun Kim、Sungsook Lee、Soon Kil Ahn、Nam Song Choi、Kyung Joo Lee

  DOI：10.1016/j.bmcl.2010.05.060

  日期：2010.11

  Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3 center dot HCl (L-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3 center dot HCl intravenously, with rapid clearance of 3 center dot HCl indicating the effective cleavage of prodrug. Compound 3 center dot HCl (CKD-516) has now been progressed to phase 1 clinical trial. (C) 2010 Published by Elsevier Ltd.
• J. Med. Chem. 2010, 53, 6337-6354
  作者：

  DOI：——

  日期：——
• US8053439B2
  申请人：——

  公开号：US8053439B2

  公开（公告）日：2011-11-08