tert-butyl 2-(3-formyl-4-methoxyphenyl)-1H-pyrrole-1-carboxylate | 872989-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: tert-butyl 2-(3-formyl-4-methoxyphenyl)-1H-pyrrole-1-carboxylate
• 英文别名: 2-(3-formyl-4-methoxy-phenyl)-pyrrole-1-carboxylic acid tert-butyl ester；1,1-Dimethylethyl 2-(3-formyl-4-methoxyphenyl)-1H-pyrrole-1-carboxylate；tert-butyl 2-(3-formyl-4-methoxyphenyl)pyrrole-1-carboxylate
• CAS: 872989-40-7
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: VQECLOKTXIRTBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(3-formyl-4-methoxyphenyl)-1H-pyrrole-1-carboxylate 、 magnesium,1,2,3-trimethoxybenzene-5-ide,bromide 以 四氢呋喃 为溶剂， 以48%的产率得到tert-butyl 2-(3-(hydroxy(3,4,5-trimethoxyphenyl)methyl)-4-methoxyphenyl)-1H-pyrrole-1-carboxylate
  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
• 作为产物：
  描述：

  5-溴-2-甲氧基苯甲醛 、 1-Boc-吡咯-2-硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 24.0h， 以39%的产率得到tert-butyl 2-(3-formyl-4-methoxyphenyl)-1H-pyrrole-1-carboxylate
  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

• 1,2-Bis-(substituted-phenyl)-2-propen-1-ones and pharmaceutical compositions thereof
  申请人：Weingarten David M.

  公开号：US20060063828A1

  公开（公告）日：2006-03-23

  The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.

  本发明涉及一般式化合物、药物组合物及其使用方法，或其药学上可接受的盐或酯，其中取代基在申请中有定义。
• [EN] 1,2-BIS-(SUBSTITUTED-PHENYL)-2-PROPEN-1-ONES AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] 1,2-BIS-(PHENYL-SUBSTITUE)-2-PROPEN-1-ONES ET DES COMPOSITIONS PHARMACEUTIQUES EN CONTENANT
  申请人：ATHEROGENICS INC

  公开号：WO2006004903A2

  公开（公告）日：2006-01-12

  The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula (I), or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.
• 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.