5-乙酰基氨基-2-甲基-n-(1r-萘-1-基-乙基)苯甲酰胺 | 1093070-14-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-乙酰基氨基-2-甲基-n-(1r-萘-1-基-乙基)苯甲酰胺
• 中文别名: PLpro抑制剂
• 英文名称: 5-acetylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
• 英文别名: 5-N-Acetylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide；PLpro inhibitor；5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide
• CAS: 1093070-14-4
• 化学式: C₂₂H₂₂N₂O₂
• 分子量: 346.429
• InChiKey: KGPYBLOBHQLIET-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-甲基-n-(1r-萘-1-基-乙基)-5-硝基苯甲酰胺 在 5%-palladium/activated carbon 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 33.0h， 生成 5-乙酰基氨基-2-甲基-n-(1r-萘-1-基-乙基)苯甲酰胺
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR TREATING RESPIRATORY DISEASES

  摘要：

  本文描述了化合物和组合物，以及使用这些化合物和组合物治疗呼吸道疾病和疾病，如严重急性呼吸综合征（SARS）的方法。

  公开号：

  US20110269834A1

文献信息

• Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2
  作者：Brian C. Sanders、Suman Pokhrel、Audrey D. Labbe、Irimpan I. Mathews、Connor J. Cooper、Russell B. Davidson、Gwyndalyn Phillips、Kevin L. Weiss、Qiu Zhang、Hugh O’Neill、Manat Kaur、Jurgen G. Schmidt、Walter Reichard、Surekha Surendranathan、Jyothi Parvathareddy、Lexi Phillips、Christopher Rainville、David E. Sterner、Desigan Kumaran、Babak Andi、Gyorgy Babnigg、Nigel W. Moriarty、Paul D. Adams、Andrzej Joachimiak、Brett L. Hurst、Suresh Kumar、Tauseef R. Butt、Colleen B. Jonsson、Lori Ferrins、Soichi Wakatsuki、Stephanie Galanie、Martha S. Head、Jerry M. Parks

  DOI：10.1038/s41467-023-37254-w

  日期：——

  interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with kinact/KI = 9,600 M−1 s−1, achieves sub-μM EC50 values against

  需要直接作用的抗病毒药物来对抗 2019 年冠状病毒病 (COVID-19)，该疾病是由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的。SARS-CoV-2 的 Nsp3 的类木瓜蛋白酶 (PLpro) 结构域对于病毒复制至关重要。此外，PLpro 通过从宿主蛋白中裂解泛素和干扰素刺激的基因 15 蛋白来调节宿主免疫反应。因此，PLpro 是小分子治疗抑制的一个有前途的靶点。在这里，我们通过将拟肽接头和反应性亲电子试剂引入到非共价 PLpro 抑制剂 GRL0617 的类似物上，设计了一系列共价抑制剂。最有效的化合物可抑制 PLpro，k inact /K I  = 9,600 M −1 s −1 ，针对哺乳动物细胞系中的三种 SARS-CoV-2 变体达到亚μM EC 50值，并且不抑制一组人类去泛素酶（DUB）抑制剂浓度 >30 μM。与 PLpro 结合的化合物的 X
• Compositions and methods for identification, assessment, prevention, and treatment of AML using USP10 biomarkers and modulators
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11136409B2

  公开（公告）日：2021-10-05

  The present invention is based, in part, on the identification of novel USP10 biomarkers and modulators, and methods of use thereof, for identifying, assessing, preventing, and treating AML.

  本发明部分基于新型 USP10 生物标记物和调节剂的鉴定及其使用方法，用于鉴定、评估、预防和治疗急性髓细胞白血病。
• Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome−Coronavirus Papain-Like Protease
  作者：Arun K. Ghosh、Jun Takayama、Yoann Aubin、Kiira Ratia、Rima Chaudhuri、Yahira Baez、Katrina Sleeman、Melissa Coughlin、Daniel B. Nichols、Debbie C. Mulhearn、Bellur S. Prabhakar、Susan C. Baker、Michael E. Johnson、Andrew D. Mesecar

  DOI：10.1021/jm900611t

  日期：2009.8.27

  We describe here the design, Synthesis, molecular modeling. and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells, Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 mu M; antiviral EC50 = 6 mu M). Interestingly. its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 mu M) and the most potent SARS antiviral activity (EC50 = 5.2 mu M) in the series, We have carried our computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.
• COMPOSITIONS AND METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND TREATMENT OF AML USING USP10 BIOMARKERS AND MODULATORS
  申请人：BUHRLAGE Sara

  公开号：US20190202929A1

  公开（公告）日：2019-07-04

  The present invention is based, in part, on the identification of novel USP10 biomarkers and modulators, and methods of use thereof, for identifying, assessing, preventing, and treating AML.
• [EN] COMPOUNDS AND METHODS FOR TREATING RESPIRATORY DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DES MALADIES RESPIRATOIRES
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2010022355A1

  公开（公告）日：2010-02-25

  Described herein are compounds and compositions, and methods for using the compounds and compositions, for treating respiratory diseases and illness, such as severe acute respiratory syndrome (SARS).