2-(4-chloro-phenyl)-4-dibromomethyl-thiazole-5-carboxylic acid methyl ester | 1048364-22-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-chloro-phenyl)-4-dibromomethyl-thiazole-5-carboxylic acid methyl ester
• 英文别名: methyl 4-(dibromomethyl)-2-(4-chlorophenyl)thiazole-5-carboxylate；methyl 2-(4-chlorophenyl)-4-(dibromomethyl)-1,3-thiazole-5-carboxylate
• CAS: 1048364-22-2
• 化学式: C₁₂H₈Br₂ClNO₂S
• 分子量: 425.528
• InChiKey: UDKITSULXSMJOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-phenyl)-4-dibromomethyl-thiazole-5-carboxylic acid methyl ester 在 氯化亚砜 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 4-(dibromomethyl)-2-(4-chlorophenyl)-N-methylthiazole-5-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Thiazoles Targeting Flavivirus Envelope Proteins

  摘要：

  A series of third-generation analogues of methyl 4-(dibromomethyl)-2-(4-chlorophenyl)thiazole-5-carboxylate (1), which had the most potent antiviral activity among the first- and second-generation compounds, have been synthesized and tested against yellow fever virus using a cell-based assay. The compounds were designed with the objectives of improving metabolic stability, therapeutic index, and antiviral potency. The biological effects of C4 and C5 substitution were examined. The methylthio ester and the dihydroxpropylamide analogues had the best antiviral potencies and improved therapeutic indices and metabolic stabilities relative to the parent compound 1.

  DOI：

  10.1021/jm1013538
• 作为产物：
  描述：

  2-(4-氯苯基)-4-甲基-1,3-噻唑-5-羧酸甲酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 反应 12.0h， 以60%的产率得到2-(4-chloro-phenyl)-4-dibromomethyl-thiazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Antiviral Agents Targeting Flavivirus Envelope Proteins

  摘要：

  Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. Inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. Virtual screening of the NCI chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. Bioassay results identified a class of thiazole compounds with antiviral potency in cell-based assays. Modification of these lead compounds led to a series of analogues with improved antiviral activity and decreased cytotoxicity. The most active compounds 11 and 36 were effective in the low micromolar concentration range in a cellular assay system.

  DOI：

  10.1021/jm800412d

文献信息

• Design, Synthesis, and Biological Evaluation of Antiviral Agents Targeting Flavivirus Envelope Proteins
  作者：Ze Li、Mansoora Khaliq、Zhigang Zhou、Carol Beth Post、Richard J. Kuhn、Mark Cushman

  DOI：10.1021/jm800412d

  日期：2008.8.1

  Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. Inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. Virtual screening of the NCI chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. Bioassay results identified a class of thiazole compounds with antiviral potency in cell-based assays. Modification of these lead compounds led to a series of analogues with improved antiviral activity and decreased cytotoxicity. The most active compounds 11 and 36 were effective in the low micromolar concentration range in a cellular assay system.
• Design, Synthesis, and Biological Evaluation of Thiazoles Targeting Flavivirus Envelope Proteins
  作者：Abdelrahman S. Mayhoub、Mansoora Khaliq、Richard J. Kuhn、Mark Cushman

  DOI：10.1021/jm1013538

  日期：2011.3.24

  A series of third-generation analogues of methyl 4-(dibromomethyl)-2-(4-chlorophenyl)thiazole-5-carboxylate (1), which had the most potent antiviral activity among the first- and second-generation compounds, have been synthesized and tested against yellow fever virus using a cell-based assay. The compounds were designed with the objectives of improving metabolic stability, therapeutic index, and antiviral potency. The biological effects of C4 and C5 substitution were examined. The methylthio ester and the dihydroxpropylamide analogues had the best antiviral potencies and improved therapeutic indices and metabolic stabilities relative to the parent compound 1.