3-((4-chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylic acid | 1429473-85-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-((4-chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylic acid
• 英文别名: 3-((4-Chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylic acid；3-(4-chlorophenyl)sulfanyl-4-methyl-1H-indole-2-carboxylic acid
• CAS: 1429473-85-7
• 化学式: C₁₆H₁₂ClNO₂S
• 分子量: 317.796
• InChiKey: KCAZHZNRZBHQFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  78.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-((4-chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 0.25h， 生成 methyl 3-((4-chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylate
  参考文献：
  名称：

  Design of Potent Poxvirus Inhibitors of the Heterodimeric Processivity Factor Required for Viral Replication

  摘要：

  Smallpox constitutes a major bioterrorism threat, which underscores the need to develop antiviral drugs for rapid response in the event of an attack. Viral processivity factors are attractive drug targets in being both specific and essential for their cognate DNA polymerases to synthesize extended strands of DNA. An in silico model of the vacinnia virus processivity factor, comprised of the A20 and D4 heterocomplex, was constructed and used for lead optimization of an indole-based scaffold identified earlier from a high-throughput screening. On the basis of this model, a new class of potent antivirals against vaccinia virus was designed and synthesized, of which two (24a and 24b) exhibited superior improvement over the parent scaffold (IC50 = 42 and 46 vs 82000 nM, respectively). The ability of 24a to suppress vaccinia DNA synthesis is supported by the inhibition of late viral gene expression, as well as by the diminished incorporation of bromodeoxyuridine into viral replication factories.

  DOI：

  10.1021/jm301735k
• 作为产物：
  描述：

  4-甲基吲哚-2-羧酸 、 4,4'-二氯二苯二硫醚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.25h， 以43%的产率得到3-((4-chlorophenyl)thio)-4-methyl-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Design of Potent Poxvirus Inhibitors of the Heterodimeric Processivity Factor Required for Viral Replication

  摘要：

  Smallpox constitutes a major bioterrorism threat, which underscores the need to develop antiviral drugs for rapid response in the event of an attack. Viral processivity factors are attractive drug targets in being both specific and essential for their cognate DNA polymerases to synthesize extended strands of DNA. An in silico model of the vacinnia virus processivity factor, comprised of the A20 and D4 heterocomplex, was constructed and used for lead optimization of an indole-based scaffold identified earlier from a high-throughput screening. On the basis of this model, a new class of potent antivirals against vaccinia virus was designed and synthesized, of which two (24a and 24b) exhibited superior improvement over the parent scaffold (IC50 = 42 and 46 vs 82000 nM, respectively). The ability of 24a to suppress vaccinia DNA synthesis is supported by the inhibition of late viral gene expression, as well as by the diminished incorporation of bromodeoxyuridine into viral replication factories.

  DOI：

  10.1021/jm301735k

文献信息

• Potent poxvirus inhibitor
  申请人：The Trustees of the University of Pennsylvania

  公开号：US09233921B2

  公开（公告）日：2016-01-12

  This invention provides compounds of formulas (I), (II), (III), and (IV) as defined in the specification, and pharmaceutical compositions comprising the same, and methods of inhibiting, treating, or abrogating a poxvirus infection in a subject using the compounds or compositions.

  本发明提供了式(I)、(II)、(III)和(IV)的化合物，如规范中所定义，并且包括相同的制药组合物，以及使用这些化合物或组合物抑制、治疗或消除主体中的痘病毒感染的方法。
• US20140343114A1
  申请人：——

  公开号：——

  公开（公告）日：——
• US9233921B2
  申请人：——

  公开号：US9233921B2

  公开（公告）日：2016-01-12
• Design of Potent Poxvirus Inhibitors of the Heterodimeric Processivity Factor Required for Viral Replication
  作者：Manunya Nuth、Hancheng Guan、Natalia Zhukovskaya、Yih Ling Saw、Robert P. Ricciardi

  DOI：10.1021/jm301735k

  日期：2013.4.25

  Smallpox constitutes a major bioterrorism threat, which underscores the need to develop antiviral drugs for rapid response in the event of an attack. Viral processivity factors are attractive drug targets in being both specific and essential for their cognate DNA polymerases to synthesize extended strands of DNA. An in silico model of the vacinnia virus processivity factor, comprised of the A20 and D4 heterocomplex, was constructed and used for lead optimization of an indole-based scaffold identified earlier from a high-throughput screening. On the basis of this model, a new class of potent antivirals against vaccinia virus was designed and synthesized, of which two (24a and 24b) exhibited superior improvement over the parent scaffold (IC50 = 42 and 46 vs 82000 nM, respectively). The ability of 24a to suppress vaccinia DNA synthesis is supported by the inhibition of late viral gene expression, as well as by the diminished incorporation of bromodeoxyuridine into viral replication factories.