(5-(1H-pyrrol-2-yl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone | 1016543-22-8

• 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: (5-(1H-pyrrol-2-yl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (5-(1H-pyrrole-2-yl)-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone；[5-(1H-pyrrol-2-yl)-2-(1,2,4-triazol-1-yl)phenyl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1016543-22-8
• 化学式: C₂₂H₂₀N₄O₄
• 分子量: 404.425
• InChiKey: HCKHGKUNWIQSLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (5-iodo-2-(1H-1,2,4-triazol-1-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone 、 1-Boc-吡咯-2-硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.25h， 以57%的产率得到(5-(1H-pyrrol-2-yl)-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：Choi Nam-Song

  公开号：US20090275575A1

  公开（公告）日：2009-11-05

  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。
• US8053439B2
  申请人：——

  公开号：US8053439B2

  公开（公告）日：2011-11-08
• [EN] BENZOPHENONE DERIVATIVES USEFUL FOR INHIBITING FORMATION OF MICROTUBULE<br/>[FR] DÉRIVÉ DE BENZOPHÉNONE CONVENANT POUR INHIBER LA FORMATION DE MICROTUBULE
  申请人：CHONG KUN DANG PHARM CORP

  公开号：WO2008038955A1

  公开（公告）日：2008-04-03

  [EN] 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.
  [FR] L'invention concerne de nouveaux dérivés de benzophénone représentés par la formule I, un sel, un hydrate ou un solvate de ce composé pharmaceutiquement acceptable, une composition pharmaceutique contenant ce composé et une utilisation de cette composition comme médicament thérapeutique. Les dérivés de benzophénone possèdent une activité d'inhibition de la formation de microtubule et peuvent être utilisés pour traiter un état prolifératif normal de tumeur maligne en tuant les cellules activement proliférantes.
• Identification of CKD-516: A Potent Tubulin Polymerization Inhibitor with Marked Antitumor Activity against Murine and Human Solid Tumors
  作者：Jaekwang Lee、Soo Jin Kim、Hojin Choi、Young Hoon Kim、In Taek Lim、Hyun-mo Yang、Chang Sik Lee、Hee Ryong Kang、Soon Kil Ahn、Seung Kee Moon、Dal-Hyun Kim、Sungsook Lee、Nam Song Choi、Kyung Joo Lee

  DOI：10.1021/jm1002414

  日期：2010.9.9

  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.