ethyl 5-chloro-3-(1-phenylcyclopropyl)-1H-indole-2-carboxylate | 1374964-75-6

• 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: ethyl 5-chloro-3-(1-phenylcyclopropyl)-1H-indole-2-carboxylate
• CAS: 1374964-75-6
• 化学式: C₂₀H₁₈ClNO₂
• 分子量: 339.821
• InChiKey: JKRDXBZSEYPGAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 5-chloro-3-(1-phenylcyclopropyl)-1H-indole-2-carboxylate 在 potassium hydroxide 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 12.0h， 生成 triethylammonium 5-chloro-3-(1-phenylcyclopropyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/ml3000462
• 作为产物：
  描述：

  二碘甲烷 、 1-tert-butyl 2-ethyl 5-chloro-3-(1-phenylvinyl)-1H-indole-1,2-dicarboxylate 在 diethylzinc 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.33h， 以37%的产率得到ethyl 5-chloro-3-(1-phenylcyclopropyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/ml3000462

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 indole based NNRTIs with improved potency against wild type and resistant HIV
  作者：Ronel Müller、Iqbal Mulani、Adriaan E. Basson、Nicole Pribut、Mohammad Hassam、Lynn Morris、Willem A.L. van Otterlo、Stephen C. Pelly

  DOI：10.1016/j.bmcl.2014.08.020

  日期：2014.9

  The human immunodeficiency virus (HIV) pandemic remains a significant problem, especially in developing nations where the social and economic impacts are severe. Until a cure or vaccine for the disease is found, a constant supply of new compounds to fill the drug development pipeline is a requirement, given the tendency for the virus to rapidly develop resistance to current therapies. Here we disclose our efforts to improve upon the efficacy of cyclopropyl-indole derivatives developed as NNRTIs in our laboratories. To this end, modifications to the functionality occupying the small Val179 pocket have resulted in nearly two orders of magnitude increase in potency. (C) 2014 Elsevier Ltd. All rights reserved.
• 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.