JLJ0240 | 1045820-10-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: JLJ0240
• 英文别名: 4-[[5-[(2,6-Difluorophenyl)methyl]oxazol-2-yl]amino]benzonitrile；4-[[5-[(2,6-difluorophenyl)methyl]-1,3-oxazol-2-yl]amino]benzonitrile
• CAS: 1045820-10-7
• 化学式: C₁₇H₁₁F₂N₃O
• 分子量: 311.291
• InChiKey: ROEXQHIMEUXNCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 4-氰基苯基异硫氰酸酯 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 JLJ0240
  参考文献：
  名称：

  Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations

  摘要：

  Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP "chlorine scan" was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC(50)) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10-20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative.

  DOI：

  10.1021/ja8019214

文献信息

• [EN] NOVEL AZOLES AND RELATED DERIVATIVES AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) IN ANTIVIRAL THERAPY (HIV)<br/>[FR] NOUVEAUX AZOLES ET DÉRIVÉS APPARENTÉS À TITRE D'INHIBITEURS NON NUCLÉOSIDIQUES DE TRANSCRIPTASE INVERSE (NNRTIS) EN THÉRAPIE ANTIVIRALE (VIH)
  申请人：UNIV YALE

  公开号：WO2009005811A1

  公开（公告）日：2009-01-08

  The present invention relates to novel heterocyclic compounds, including oxadiazole compounds, pharmaceutical compositions and their use in the inhibition of reverse transcriptase and the treatment of HIV (1 and 2) infections, AIDS and ARC and other viral infections.

  本发明涉及新颖的杂环化合物，包括噁二唑化合物，药物组合物及其在抑制逆转录酶以及治疗HIV（1和2）感染、艾滋病和ARC以及其他病毒感染中的用途。
• Novel azoles and related derivatives as non-nucleoside reverse transcriptase inhibitors (nnrtis) in antiviral therapy (hiv)
  申请人：Jorgensen William L.

  公开号：US20100168190A1

  公开（公告）日：2010-07-01

  The present invention relates to novel heterocyclic compounds, including oxadiazole compounds, pharmaceutical compositions and their use in the inhibition of reverse transcriptase and the treatment of HIV (1 and 2) infections, AIDS and ARC and other viral infections.

  本发明涉及新型杂环化合物，包括噁唑化合物，制药组合物及其在抑制反转录酶和治疗HIV（1和2）感染，艾滋病和ARC以及其他病毒感染方面的用途。
• Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations
  作者：Jacob G. Zeevaart、Ligong Wang、Vinay V. Thakur、Cheryl S. Leung、Julian Tirado-Rives、Christopher M. Bailey、Robert A. Domaoal、Karen S. Anderson、William L. Jorgensen

  DOI：10.1021/ja8019214

  日期：2008.7.1

  Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP "chlorine scan" was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC(50)) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10-20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative.
• US8492415B2
  申请人：——

  公开号：US8492415B2

  公开（公告）日：2013-07-23
• Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency
  作者：Mariela Bollini、Ricardo Gallardo-Macias、Krasimir A. Spasov、Julian Tirado-Rives、Karen S. Anderson、William L. Jorgensen

  DOI：10.1016/j.bmcl.2012.11.115

  日期：2013.2

  Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs le and if with 1-7 nM potency towards both the wild-type virus and a Tyr181C variant. (C) 2012 Elsevier.Ltd. All rights reserved.