1-methyl-3-(trifluoromethyl)-N-[4-(pyrrolidinylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide | 515120-72-6

• 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: 1-methyl-3-(trifluoromethyl)-N-[4-(pyrrolidinylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide
• 英文别名: 1-methyl-N-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide；2-methyl-N-(4-pyrrolidin-1-ylsulfonylphenyl)-5-(trifluoromethyl)pyrazole-3-carboxamide
• CAS: 515120-72-6
• 化学式: C₁₆H₁₇F₃N₄O₃S
• mdl: MFCD03758070
• 分子量: 402.397
• InChiKey: GEBLSGPNGXVEHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-甲基-3-三氟甲基-1H-吡唑 在 N,N-二甲基甲酰胺 吡啶 、 正丁基锂 、 草酰氯 、 二异丙胺 作用下， 以 二氯甲烷 为溶剂， 反应 23.0h， 生成 1-methyl-3-(trifluoromethyl)-N-[4-(pyrrolidinylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  PARAMYXOVIRUS FAMILY INHIBITORS AND METHODS OF USE THEREOF

  摘要：

  本公开的实施例包括用于识别化合物或化合物的方法，这些化合物在治疗副黏病毒感染方面作为治疗剂有用，用于麻疹治疗的化合物，以及用于识别能够抑制副黏病毒增殖的化合物的高通量筛选方法。

  公开号：

  US20110160188A1

文献信息

• Nonnucleoside Inhibitor of Measles Virus RNA-Dependent RNA Polymerase Complex Activity
  作者：Laura K. White、Jeong-Joong Yoon、Jin K. Lee、Aiming Sun、Yuhong Du、Haian Fu、James P. Snyder、Richard K. Plemper

  DOI：10.1128/aac.00289-07

  日期：2007.7

  Paramyxoviruses comprise several major human pathogens. Although a live-attenuated vaccine protects against measles virus (MV), a member of the paramyxovirus family, the virus remains a principal cause of worldwide mortality and accounts for approximately 21 million cases and 300,000 to 400,000 deaths annually. The development of novel antivirals that allow improved case management of severe measles and silence viral outbreaks is thus highly desirable. We have previously described the development of novel MV fusion inhibitors. The potential for preexisting or emerging resistance in the field constitutes the rationale for the identification of additional MV inhibitors with a diverse target spectrum. Here, we report the development and implementation of a cell-based assay for high-throughput screening of MV antivirals, which has yielded several hit candidates. Following confirmation by secondary assays and chemical synthesis, the most potent hit was found to act as a target-specific inhibitor of MV replication with desirable drug-like properties. The compound proved highly active against multiple primary isolates of diverse MV genotypes currently circulating worldwide, showing active concentrations of 35 to 145 nM. Significantly, it does not interfere with viral entry and lacks cross-resistance with the MV fusion inhibitor class. Mechanistic characterization on a subinfection level revealed that the compound represents a first-in-class nonnucleoside inhibitor of MV RNA-dependent RNA polymerase complex activity. Singly or in combination with the fusion inhibitors, this novel compound class has high developmental potential as a potent therapeutic against MV and will likely further the mechanistic characterization of the viral polymerase complex.

  摘要 副黏液病毒是几种主要的人类病原体。尽管减毒活疫苗可预防副黏液病毒家族成员之一的麻疹病毒（MV），但该病毒仍是导致全球死亡的主要原因，每年约有 2100 万例病例，造成 30 万至 40 万人死亡。因此，开发新型抗病毒药物以改善严重麻疹和沉默病毒爆发的病例管理是非常有必要的。我们以前曾介绍过新型麻疹病毒融合抑制剂的开发情况。由于该领域可能存在或正在出现耐药性，因此我们需要确定更多具有不同靶点谱的中链抑制剂。在此，我们报告了一种基于细胞的检测方法的开发和实施情况，该方法用于高通量筛选中毒性病毒抗病毒药物，目前已产生了几种候选药物。经过二次测定和化学合成的确认，我们发现最有效的候选化合物是一种靶向特异的病毒复制抑制剂，具有理想的类药物特性。事实证明，该化合物对目前全球流行的不同 MV 基因型的多个原代分离物具有很高的活性，活性浓度在 35 到 145 nM 之间。值得注意的是，它不会干扰病毒的进入，也不会与病毒融合抑制剂产生交叉耐药性。在亚感染水平上进行的机理分析表明，该化合物是第一类非核苷类 MV RNA 依赖性 RNA 聚合酶复合物活性抑制剂。无论是单独使用还是与融合抑制剂联合使用，这种新型化合物类别都具有很高的发展潜力，可作为抗 MV 的强效疗法，并有可能进一步推动病毒聚合酶复合物的机理研究。
• Paramyxovirus family inhibitors and methods of use thereof
  申请人：Emory University

  公开号：EP2422790A1

  公开（公告）日：2012-02-29

  The present invention provides compounds for the treatment of measles.

  本发明提供了用于治疗麻疹的化合物。
• Potent Non-Nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase Complex
  作者：Aiming Sun、Jeong-Joong Yoon、Yan Yin、Andrew Prussia、Yutao Yang、Jaeki Min、Richard K. Plemper、James P. Snyder

  DOI：10.1021/jm701239a

  日期：2008.7

  Measles virus (MV) is one of the most infectious pathogens known. In spite of the existence of a vaccine, approximately 350000 deaths/year result from MV or associated complications. Antimeasles compounds Could conceivably diminish these statistics and provide a therapy that complements vaccine treatment. We recently described a high-throughput screening hit compound 1 (16677) against MV-infected cells with the capacity to eliminate viral reproduction at 250 nM by inhibiting the action of the virus's RNA-dependent RNA polymerase complex (RdRp). The compound, 1-methyl-3-(trifluoroi-nethyl)-N-[4-sulfonylphenyl]-1H-pyrazole-5-carboxamide, 1 carries a critical CF3 moiety on the 1,2-pyrazole ring. Elaborating on the preliminary structure-activity (SAR) study, the present work presents the synthesis and SAR of a much broader range of low nanomolar nonpeptidic MV inhibitors and speculates on the role of the CF3 functionality.
• MYXOVIRUS THERAPEUTICS, COMPOUNDS, AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP2771324B1

  公开（公告）日：2017-02-01
• US8729059B2
  申请人：——

  公开号：US8729059B2

  公开（公告）日：2014-05-20