11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene | 1049088-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene
• 英文别名: [5-(4-Benzyloxy-2-fluoro-phenyl)-10-hydroxy-2,2-dimethyl-4,4-dioxo-1,3,5,11-tetrahydrothiopyrano[2,3-c][1,5]benzodiazepin-6-yl]-(6-methyl-2-pyridyl)methanone；[5-(2-fluoro-4-phenylmethoxyphenyl)-10-hydroxy-2,2-dimethyl-4,4-dioxo-1,3,5,11-tetrahydrothiopyrano[2,3-c][1,5]benzodiazepin-6-yl]-(6-methylpyridin-2-yl)methanone
• CAS: 1049088-76-7
• 化学式: C₃₄H₃₂FN₃O₅S
• 分子量: 613.71
• InChiKey: CLEOWFBQYYBWRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene 生成 (S)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene 、 (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene
  参考文献：
  名称：

  WO2008/99020

  摘要：

  公开号：
• 作为产物：
  描述：

  6-甲基吡啶甲酰氯 、 11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene 在 N,N-二异丙基乙胺 、 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以82%的产率得到11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-1,1-dioxo-10-(6-methyl-2-pyridylcarbonyl)-1,2,3,4,5,11-hexahydro-1λ6-thia-5,10-diazadibenzo[a,d]cycloheptene
  参考文献：
  名称：

  Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase

  摘要：

  HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.

  DOI：

  10.1021/jm9005548

文献信息

• WO2008/99020
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] 1,1-DIOXO-1-THIA-5,10-DIAZADIBENZOCYCLOHEPTENES USEFUL AS HEPATITIS C VIRUS INHIBITORS<br/>[FR] 1,1-DIOXO-1-THIA-5,10-DIAZADIBENZOCYCLOHEPTÈNES UTILES COMME INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：TIBOTEC PHARM LTD

  公开号：WO2008099020A1

  公开（公告）日：2008-08-21

  [EN] Inhibitors of HCV replication of formula (I) the stereoisomers, prodrugs, tautomers, racemics, salts, hydrates or solvates thereof wherein R^1a; R^1b R²; R³; R^4a and R^4b have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.
  [FR] L'invention porte sur des inhibiteurs de réplication du VHC de formule (I), sur les stéréoisomères, les promédicaments, les tautomères, les racémiques, les sels, les hydrates ou les solvates de ceux-ci. Dans la formule, R^1a; R^1b ; R²; R³; R^4a et R^4b ont la signification définie dans les revendications. La présente invention porte également sur des procédés de préparation desdits composés, sur des compositions pharmaceutiques les contenant et sur leur utilisation dans la thérapie du VHC.
• Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase
  作者：Koen Vandyck、Maxwell D. Cummings、Origène Nyanguile、Carlo W. Boutton、Sandrine Vendeville、David McGowan、Benoit Devogelaere、Katie Amssoms、Stefaan Last、Klara Rombauts、Abdellah Tahri、Pedro Lory、Lili Hu、Derek A. Beauchamp、Kenny Simmen、Pierre Raboisson

  DOI：10.1021/jm9005548

  日期：2009.7.23

  HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.