1-(5-Bromo-2-pyridyl)-3-[2-(1-piperidyl)ethyl]thiourea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(5-Bromo-2-pyridyl)-3-[2-(1-piperidyl)ethyl]thiourea
• 英文别名: 1-(5-bromopyridin-2-yl)-3-(2-piperidin-1-ylethyl)thiourea
• 化学式: C₁₃H₁₉BrN₄S
• 分子量: 343.291
• InChiKey: OJYPMRCJFGEHKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  72.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(2-氨乙基)哌啶 、 imidazole-1-carbothionic acid (5-bromopyridin-2-yl)amide 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 1-(5-Bromo-2-pyridyl)-3-[2-(1-piperidyl)ethyl]thiourea
  参考文献：
  名称：

  Structure-based design of N-[2-(1-piperidinylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase

  摘要：

  A novel computer model of the HIV reverse transcriptase (RT) non-nucleoside inhibitor (NNI) binding pocket, which was generated using high resolution crystal structure information from 9 individual RT/NNI complexes, revealed previously unrecognized ligand derivatization sites for phenethylthiazolylthiourea (PETT) derivatives. Spatial gaps surrounding the pyridyl ring of the active PETT derivative trovirdine were discovered during modeling procedures. Docking studies using the computer-generated model of the binding pocket (composite binding pocket) suggested that the replacement of the planar pyridyl ring of trovirdine with a nonplanar piperidinyl or piperazinyl ring, which occupy larger volumes, would better fill the spacious Wing 2 region of the butterfly-shaped NNI binding pocket. The anti-HIV activity of the synthesized heterocyclic compounds N-[2-(1-piperidinylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N'-[2(5-bromopyridyl)]-thiourea was examined in HTLVIIIB-infected peripheral blood mononuclear cells. Both compounds were more potent than trovirdine and abrogated HIV replication at nanomolar concentrations without any evidence of cytotoxicity. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00384-9

文献信息

• Nonnucleoside inhibitors of reverse transcriptase for the treatment of HIV infection
  申请人：Parker Hughes Institute

  公开号：EP1528057A1

  公开（公告）日：2005-05-04

  Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. These novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-I). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzy-loxopyrimidine (DABO), and of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes. The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.

  本发明描述了对 HIV 逆转录酶（RT）具有强效抑制作用的新型化合物。这些新型化合物还能抑制逆转录病毒（如人类免疫缺陷病毒-1（HIV-I））的复制。本发明的新型化合物包括苯乙基噻唑基硫脲（PETT）、二氢烷氧基苄基环嘧啶（DABO）和 1-[(2-羟基乙氧基)甲基]-6-(苯硫基)胸腺嘧啶（HEPT）的类似物和衍生物。本发明还提供了一种复合 HIV 逆转录酶（RT）非核苷抑制剂（NNI）结合袋，该结合袋由多个 NNI-RT 复合物复合而成。复合 RT-NNI 结合袋为设计和鉴定新型、强效的逆转录酶抑制剂提供了独特而有用的工具。
• Nonnucleoside inhibitors of reverse transcriptase, composite binding pocket and methods for use thereof
  申请人：Vig Rakesh

  公开号：US20050153995A1

  公开（公告）日：2005-07-14

  Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. Thes novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-1). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzyloxopyrimidine (DABO), and of 1-[( 2 -hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.

  本发明描述了对 HIV 逆转录酶（RT）具有强效抑制作用的新型化合物。这些新型化合物还能抑制逆转录病毒（如人类免疫缺陷病毒-1（HIV-1））的复制。本发明的新型化合物包括苯乙基噻唑基硫脲（PETT）、二氢烷氧基苄氧基嘧啶（DABO）和 1-[( 2 -羟乙氧甲基]-6-(苯硫基)胸腺嘧啶 (HEPT)。此外，本发明还提供了一种由多种 NNI-RT 复合物复合而成的复合 HIV 逆转录酶（RT）非核苷抑制剂（NNI）结合袋。这种复合 RT-NNI 结合袋为设计和鉴定新型、强效的逆转录酶抑制剂提供了一种独特而有用的工具。
• NONNUCLEOSIDE INHIBITORS OF REVERSE TRANSCRIPTASE FOR THE TREATMENT OF HIV-INFECTION
  申请人：Parker Hughes Institute

  公开号：EP1064263B1

  公开（公告）日：2005-12-07
• THIOPHENE-ETHYL THIOUREA COMPOUNDS AND USE IN THE TREATMENT OF HIV
  申请人：Parker Hughes Institute

  公开号：EP1194427B1

  公开（公告）日：2003-03-05
• US5998411A
  申请人：——

  公开号：US5998411A

  公开（公告）日：1999-12-07