3-(4-amino-2-tert-butyl-5-methyl-phenylsulfanyl)-6-cyclopentyl-4-hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-5,6-dihydro-pyran-2-one

• 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: 3-(4-amino-2-tert-butyl-5-methyl-phenylsulfanyl)-6-cyclopentyl-4-hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-5,6-dihydro-pyran-2-one
• 英文别名: 3-(4-Amino-2-tert-butyl-5-methyl-phenylsulfanyl)-6-cyclopentyl-4-hydroxy-6-[2-(4-hydroxyphenyl)ethyl]-5,6-dihydro-pyran-2-one；5-(4-amino-2-tert-butyl-5-methyl-phenyl)sulfanyl-2-cyclopentyl-4-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]-3H-pyran-6-one；5-(4-amino-2-tert-butyl-5-methylphenyl)sulfanyl-2-cyclopentyl-4-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]-3H-pyran-6-one
• 化学式: C₂₉H₃₇NO₄S
• 分子量: 495.683
• InChiKey: ZEBFKFGJWHOOST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-叔丁基甲苯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 KH₂PO₄ buffer 、 DL-dithiothreitol 、 硫酸 、 氢气 、 溴 、 硝酸 、 potassium carbonate 、 三乙胺 、 sodium bromide 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-amino-2-tert-butyl-5-methyl-phenylsulfanyl)-6-cyclopentyl-4-hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-5,6-dihydro-pyran-2-one
  参考文献：
  名称：

  Nonpeptidic HIV protease inhibitors: 6-alkyl-5, 6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl, 5-methylphenyl thio) moiety: Antiviral activities and pharmacokinetic properties

  摘要：

  Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.

  DOI：

  10.1016/s0960-894x(99)00237-1

文献信息

• [EN] INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME<br/>[FR] INHIBITEURS DE L'ARN POLYMERASE ARN-DEPENDANTE DU VIRUS DE L'HEPATITE C ET COMPOSITIONS ET TRAITEMENTS UTILISANT CETTE POLYMERASE
  申请人：PFIZER

  公开号：WO2003095441A1

  公开（公告）日：2003-11-20

  Compounds of formula (I) are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus.

  化合物的化学式（I）是丙型肝炎病毒（HCV）RNA依赖性RNA聚合酶（RdRp）抑制剂，对感染丙型肝炎病毒的人进行治疗和预防性治疗具有用处。
• Hepatitis C virus (HCV) NS5B RNA polymerase and mutants thereof
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1256628A9

  公开（公告）日：2003-04-16

  The present invention generally relates to viral RNA polymerases, which are essential to viral reproduction and propagation in a host. Viral RNA polymerases are known to play a role in the replication of the virus once it has infected its host. The present invention relates to mutants of native Hepatitis C Virus (HCV) RNA polymerase, said mutants imparting improved crystallization properties of the enzyme and enzyme/compound complexes. The present invention also relates to the isolation and identification of an allosteric binding cleft within the HCV NS5B RNA polymerase and its use in the discovery, identification, and characterization of inhibitors of same.

  本发明通常涉及病毒RNA聚合酶，该酶对于病毒在宿主体内的复制和传播至关重要。已知病毒RNA聚合酶在病毒感染宿主后的复制中发挥作用。本发明涉及天然丙型肝炎病毒（HCV）RNA聚合酶的突变体，该突变体赋予酶和酶/化合物复合物改进的结晶性能。本发明还涉及在HCV NS5B RNA聚合酶中分离和鉴定一个变构结合裂隙及其在发现、鉴定和表征其抑制剂方面的应用。
• Hepatitis c virus (hcv) ns5b rna polymerase and mutants thereof
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1256628A2

  公开（公告）日：2002-11-13

  The present invention generally relates to viral RNA polymerases, which are essential to viral reproduction and propagation in a host. Viral RNA polymerases are known to play a role in the replication of the virus once it has infected its host. The present invention relates to mutants of native Hepatitis C Virus (HCV) RNA polymerase, said mutants imparting improved crystallization properties of the enzyme and enzyme/compound complexes. The present invention also relates to the isolation and identification of an allosteric binding cleft within the HCV NS5B RNA polymerase and its use in the discovery, identification, and characterization of inhibitors of same.

  本发明一般涉及病毒 RNA 聚合酶，它对病毒在宿主体内的繁殖和传播至关重要。 已知病毒 RNA 聚合酶在病毒感染宿主后的复制过程中发挥作用。 本发明涉及原生丙型肝炎病毒（HCV）RNA 聚合酶的突变体，所述突变体可改善酶和酶/化合物复合物的结晶特性。 本发明还涉及分离和鉴定 HCV NS5B RNA 聚合酶内的异生结合裂隙，并将其用于发现、鉴定和表征其抑制剂。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US20040023958A1

  公开（公告）日：2004-02-05

  Compounds of formula I are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus. 1

  式 I 的化合物是丙型肝炎病毒（HCV）RNA 依赖性 RNA 聚合酶（RdRp）抑制剂，可用于丙型肝炎病毒感染者的治疗和预防。 1