N-(4-((2-((2-hydroxyethoxy)methyl)piperidin-1-yl)sulfonyl)phenyl)-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide | 1374006-98-0

• 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: N-(4-((2-((2-hydroxyethoxy)methyl)piperidin-1-yl)sulfonyl)phenyl)-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide
• 英文别名: N-(4-((2-((2-hydroxyethoxy)methyl)piperidin-1-yl)sulfonyl)phenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide；N-[4-[2-(2-hydroxyethoxymethyl)piperidin-1-yl]sulfonylphenyl]-2-methyl-5-(trifluoromethyl)pyrazole-3-carboxamide
• CAS: 1374006-98-0
• 化学式: C₂₀H₂₅F₃N₄O₅S
• 分子量: 490.504
• InChiKey: JAWYGRCMSGZOEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-哌啶甲醇 在 dirhodium tetraacetate 、 sodium tetrahydroborate 、 草酰氯 、 palladium on activated charcoal 、 水 、 氢气 、 sodium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 20.08h， 生成 N-(4-((2-((2-hydroxyethoxy)methyl)piperidin-1-yl)sulfonyl)phenyl)-1-methyl-3-(trifluoromethyl)pyrazole-5-carboxamide
  参考文献：
  名称：

  Non-nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase: Synthesis, Structure–Activity Relationships, and Pharmacokinetics

  摘要：

  The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC50 = 60 nM) with an aqueous solubility of approximately 60 mu g/mL. The agent shows a 10-fold exposure (AUC/C-max) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.

  DOI：

  10.1021/jm201699w

文献信息

• [EN] MYXOVIRUS THERAPEUTICS, COMPOUNDS, AND USES RELATED THERETO<br/>[FR] THÉRAPEUTIQUE DES MYXOVIRUS, COMPOSÉS ET UTILISATIONS S'Y RAPPORTANT
  申请人：UNIV EMORY

  公开号：WO2013063012A1

  公开（公告）日：2013-05-02

  This disclosure relates to antiviral compounds disclosed herein and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions. Typically, the pharmaceutical composition comprises a compound of formula I: Formula I, or salt, prodrug, or ester thereof wherein X, Y, and R1 and R10 to R13 are described herein.

  本公开涉及此处披露的抗病毒化合物及其相关用途。在某些实施例中，该公开涉及药物组合物。通常，药物组合物包括式I的化合物：式I，或其盐、前药或酯，其中X、Y、以及R1和R10到R13如本文所述。
• MYXOVIRUS THERAPEUTICS, COMPOUNDS, AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP2771324A1

  公开（公告）日：2014-09-03
• MYXOVIRUS THERAPEUTICS, COMPOUNDS, AND USES RELATED THERETO
  申请人：EMORY UNIVERSITY

  公开号：US20140329817A1

  公开（公告）日：2014-11-06

  This disclosure relates to antiviral compounds disclosed herein and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions. Typically, the pharmaceutical composition comprises a compound of formula I: Formula I, or salt, prodrug, or ester thereof wherein X, Y, and R 1 and R 10 to R 13 are described herein.
• Myxovirus Therapeutics, Compounds, and Uses Related Thereto
  申请人：Emory University

  公开号：US20160310511A1

  公开（公告）日：2016-10-27

  This disclosure relates to antiviral compounds disclosed herein and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions. Typically, the pharmaceutical composition comprises a compound of formula I: or salt, prodrug, or ester thereof wherein X, Y, and R 1 and R 10 to R 13 are described herein
• US9499489B2
  申请人：——

  公开号：US9499489B2

  公开（公告）日：2016-11-22