1-tert-butyl 2-ethyl 3-benzoyl-5-chloro-1H-indole-1,2-dicarboxylate | 1374964-63-2

• 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: 1-tert-butyl 2-ethyl 3-benzoyl-5-chloro-1H-indole-1,2-dicarboxylate
• 英文别名: 1-O-tert-butyl 2-O-ethyl 3-benzoyl-5-chloroindole-1,2-dicarboxylate
• CAS: 1374964-63-2
• 化学式: C₂₃H₂₂ClNO₅
• 分子量: 427.884
• InChiKey: GFKBDAGMBOGZOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  74.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 2-ethyl 3-benzoyl-5-chloro-1H-indole-1,2-dicarboxylate 在 劳森试剂 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.5h， 生成 1-tert-butyl 2-ethyl 5-chloro-3-(mercapto(phenyl)methyl)-1H-indole-1,2-dicarboxylate
  参考文献：
  名称：

  Novel indole sulfides as potent HIV-1 NNRTIs

  摘要：

  In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted S(N)1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.006
• 作为产物：
  描述：

  5-氯吲哚-2-羧酸乙酯 在 4-二甲氨基吡啶 、 aluminum (III) chloride 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 5.5h， 生成 1-tert-butyl 2-ethyl 3-benzoyl-5-chloro-1H-indole-1,2-dicarboxylate
  参考文献：
  名称：

  Novel indole sulfides as potent HIV-1 NNRTIs

  摘要：

  In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted S(N)1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.006

文献信息

• [EN] SUBSTITUTED INDOLES AND THEIR USE AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS<br/>[FR] INDOLES SUBSTITUÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS NON-NUCLÉOSIDIQUES DE LA TRANSCRIPTASE INVERSE
  申请人：UNIV STELLENBOSCH

  公开号：WO2015044928A1

  公开（公告）日：2015-04-02

  Compounds of Formula I or pharmaceutically acceptable salts thereof are claimed, wherein R1 is an ester, amide or a heterocycle; R2 is C or N; R3 is a methoxy or ethoxy group, an alkyl group or a heterocyclic group; R4 is a substituted or unsubstituted phenyl or heteroaromatic group; and R5 is a halide or a nitrile. The use of these compounds as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for inhibiting or treating HIV infection or AIDS is also described.

  本发明涉及化合物I的配方或其药学上可接受的盐，其中R1是酯、酰胺或杂环；R2是C或N；R3是甲氧基或乙氧基基团、烷基或杂环基团；R4是取代或未取代的苯基或杂环芳基；R5是卤素或腈基。本发明还描述了这些化合物作为非核苷类逆转录酶抑制剂（NNRTIs）用于抑制或治疗HIV感染或艾滋病的用途。
• Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Mohammad Hassam、Adriaan E. Basson、Dennis C. Liotta、Lynn Morris、Willem A. L. van Otterlo、Stephen C. Pelly

  DOI：10.1021/ml3000462

  日期：2012.6.14

  The HIV pandemic represents one of the most serious diseases to face mankind in both a social and economic context, with many developing nations being the worst afflicted. Due to ongoing resistance issues associated with the disease, the design and synthesis of anti-HIV agents presents a constant challenge for medicinal chemists. Utilizing molecular modeling, we have designed a series of novel cyclopropyl indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors and carried out their preparation. These compounds facilitate a double hydrogen bonding interaction to Lys101 and efficiently occupy the hydrophobic pockets in the regions of Tyr181/188 and Val179. Several of these compounds inhibited HIV replication as effectively as nevirapine when tested in a phenotypic assay.