1-[(5-methanesulfonamidoindol-2-yl)carbonyl]-4-[N-ethyl-N-[3-[(1,1-dimethylethyl)amino]-2-pyridinyl]amino]piperidine | 177577-60-5

• 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-[(5-methanesulfonamidoindol-2-yl)carbonyl]-4-[N-ethyl-N-[3-[(1,1-dimethylethyl)amino]-2-pyridinyl]amino]piperidine
• 英文别名: N-[2-[4-[[3-(tert-butylamino)pyridin-2-yl]-ethylamino]piperidine-1-carbonyl]-1H-indol-5-yl]methanesulfonamide
• CAS: 177577-60-5
• 化学式: C₂₆H₃₆N₆O₃S
• 分子量: 512.676
• InChiKey: BUYBIVUAJHJDTC-UHFFFAOYSA-N

物化性质

• 沸点：
  734.2±70.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 在 platinum(IV) oxide 、 palladium on activated charcoal 吡啶 、 lithium aluminium tetrahydride 、 氢气 、 4-甲基苯磺酸吡啶 、 potassium carbonate 、 N,N'-羰基二咪唑 、 lithium bromide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 96.0h， 生成 1-[(5-methanesulfonamidoindol-2-yl)carbonyl]-4-[N-ethyl-N-[3-[(1,1-dimethylethyl)amino]-2-pyridinyl]amino]piperidine
  参考文献：
  名称：

  Targeting Delavirdine/Atevirdine Resistant HIV-1:  Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHPSs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.

  DOI：

  10.1021/jm960158n

文献信息

• Methods and compositions for the treatment or prevention of human immunodeficiency virus and related conditions using cyclooxygenase-2 selective inhibitors and antiviral agents
  申请人：Maziasz Timothy

  公开号：US20050026902A1

  公开（公告）日：2005-02-03

  The present invention provides compositions and methods for the treatment of human immunodeficiency virus (HIV) infection as well as HIV associated diseases and related disorders. More particularly, the invention provides a combination therapy for the treatment of HIV infection as well as HIV associated diseases and related disorders comprising the administration to a subject of an anti-human immunodeficiency virus agent in combination with a cyclooxygenase-2 selective inhibitor or an isomer or a pharmaceutically acceptable salt, ester, or prodrug thereof.

  本发明提供了治疗人类免疫缺陷病毒（HIV）感染以及HIV相关疾病和相关紊乱的组合物和方法。更具体地说，本发明提供了一种治疗HIV感染以及HIV相关疾病和相关紊乱的组合疗法，包括向受试者施用抗人类免疫缺陷病毒制剂与环氧化酶-2选择性抑制剂或其异构体或其药学上可接受的盐、酯或原药组合。
• Targeting Delavirdine/Atevirdine Resistant HIV-1:  Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors
  作者：Donna L. Romero、Robert A. Olmsted、Toni Jo Poel、Raymond A. Morge、Carolyn Biles、Barbara J. Keiser、Laurice A. Kopta、Jan M. Friis、John D. Hosley、Kevin J. Stefanski、Donn G. Wishka、David B. Evans、Joel Morris、Randy G. Stehle、Satish K. Sharma、Yoshihiko Yagi、Richard L. Voorman、Wade J. Adams、W. Gary Tarpley、Richard C. Thomas

  DOI：10.1021/jm960158n

  日期：1996.1.1

  A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHPSs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.