JZ-1-96-2-1 | 1609571-22-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: JZ-1-96-2-1
• 英文别名: 4-[2-(3-chlorophenyl)-ethyl]-5-hydroxy-3-(4-nitrophenyl)-pyrazole-1-carbothioic acid amide
• CAS: 1609571-22-3
• 化学式: C₁₈H₁₅ClN₄O₃S
• 分子量: 402.861
• InChiKey: VEOHSTXVKNOZKD-UHFFFAOYSA-N

物化性质

• 沸点：
  636.2±65.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  107.21
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  对硝基苯甲酰醋酸乙酯 在 potassium carbonate 、 sodium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 生成 JZ-1-96-2-1
  参考文献：
  名称：

  Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists

  摘要：

  The HIV-1 Nef accessory factor enhances viral replication and promotes immune system evasion of HIV-infected cells, making it an attractive target for drug discovery. Recently we described a novel class of diphenylpyrazolodiazene compounds that bind directly to Nef in vitro and inhibit Nef-dependent HIV-1 infectivity and replication in cell culture. However, these first-generation Nef antagonists have several structural liabilities, including an azo linkage that led to poor oral bioavailability. The azo group was therefore replaced with either a one- or two-carbon linker. The resulting set of non-azo analogs retained nanomolar binding affinity for Nef by surface plasmon resonance, while inhibiting HIV-1 replication with micromolar potency in cell-based assays without cytotoxicity. Computational docking studies show that these non-azo analogs occupy the same predicted binding site within the HIV-1 Nef dimer interface as the original azo compound. Computational methods also identified a hot spot for inhibitor binding within this site that is defined by conserved HIV-1 Nef residues Asp108, Leu112, and Pro122. Pharmacokinetic evaluation of the non-azo B9 analogs in mice showed that replacement of the azo linkage dramatically enhanced oral bioavailability without substantially affecting plasma half-life or clearance. The improved oral bioavailability of non-azo diphenylpyrazolo Nef antagonists provides a starting point for further drug lead optimization in support of future efficacy testing in animal models of HIV/AIDS. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.043

文献信息

• Compositions and Kits Pertaining to Analyte Determination
  申请人：Pappin Darryl J.C.

  公开号：US20110217720A1

  公开（公告）日：2011-09-08

  This invention pertains to methods, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.

  本发明涉及使用独特的标记试剂或一组独特的标记试剂进行质量分析以确定分析物的方法、试剂盒和/或组合物。这些标记试剂可以是同分异构体或同质异构体，并可用于生成适用于标记分析的混合物。
• COMPOUNDS FOR TREATING HIV AND METHODS FOR USING THE COMPOUNDS
  申请人：UNIVERSITY OF PITTSBURGH-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：US20150291534A1

  公开（公告）日：2015-10-15

  Disclosed herein are embodiments of a compound capable of treating HIV. In particular disclosed embodiments, the compound is capable of inhibiting Nef, such as by acting as antagonists of HIV Nef function. Also disclosed are embodiments of a method of making the compound, embodiments of a method of using the compound, and embodiments of a method of identifying HIV Nef antagonists. The disclosed compound may be used alone or in combination with other pharmacologically active agents in order to promote reducing drug resistance and/or cumulative toxicity.
• US9695127B2
  申请人：——

  公开号：US9695127B2

  公开（公告）日：2017-07-04
• [EN] COMPOUNDS FOR TREATING HIV AND METHODS FOR USING THE COMPOUNDS<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DU VIH ET PROCÉDÉS D'UTILISATION DES COMPOSÉS
  申请人：UNIV PITTSBURGH

  公开号：WO2014074628A1

  公开（公告）日：2014-05-15

  Disclosed herein are embodiments of a compound capable of treating HIV. In particular disclosed embodiments, the compound is capable of inhibiting Nef, such as by acting as antagonists of HIV Nef function. Also disclosed are embodiments of a method of making the compound, embodiments of a method of using the compound, and embodiments of a method of identifying HIV Nef antagonists. The disclosed compound may be used alone or in combination with other pharmacologically active agents in order to promote reducing drug resistance and/or cumulative toxicity.
• Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists
  作者：Lori A. Emert-Sedlak、H. Marie Loughran、Haibin Shi、John L. Kulp、Sherry T. Shu、Jielu Zhao、Billy W. Day、Jay E. Wrobel、Allen B. Reitz、Thomas E. Smithgall

  DOI：10.1016/j.bmcl.2016.01.043

  日期：2016.3

  The HIV-1 Nef accessory factor enhances viral replication and promotes immune system evasion of HIV-infected cells, making it an attractive target for drug discovery. Recently we described a novel class of diphenylpyrazolodiazene compounds that bind directly to Nef in vitro and inhibit Nef-dependent HIV-1 infectivity and replication in cell culture. However, these first-generation Nef antagonists have several structural liabilities, including an azo linkage that led to poor oral bioavailability. The azo group was therefore replaced with either a one- or two-carbon linker. The resulting set of non-azo analogs retained nanomolar binding affinity for Nef by surface plasmon resonance, while inhibiting HIV-1 replication with micromolar potency in cell-based assays without cytotoxicity. Computational docking studies show that these non-azo analogs occupy the same predicted binding site within the HIV-1 Nef dimer interface as the original azo compound. Computational methods also identified a hot spot for inhibitor binding within this site that is defined by conserved HIV-1 Nef residues Asp108, Leu112, and Pro122. Pharmacokinetic evaluation of the non-azo B9 analogs in mice showed that replacement of the azo linkage dramatically enhanced oral bioavailability without substantially affecting plasma half-life or clearance. The improved oral bioavailability of non-azo diphenylpyrazolo Nef antagonists provides a starting point for further drug lead optimization in support of future efficacy testing in animal models of HIV/AIDS. (C) 2016 Elsevier Ltd. All rights reserved.