5-chloro-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methyl-benzenesulfonic acid | 946066-41-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 5-chloro-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methyl-benzenesulfonic acid
• 英文别名: 5-chloro-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylbenzenesulfonic acid
• CAS: 946066-41-7
• 化学式: C₂₂H₁₈ClNO₅S
• 分子量: 443.908
• InChiKey: NJYZVNHLHRVJMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methyl-benzenesulfonic acid 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (4-chloro-2-chlorosulfonyl-5-methyl-phenyl)-carbamic acid 9H-fluoren-9-ylmethyl ester
  参考文献：
  名称：

  Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site

  摘要：

  Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.

  DOI：

  10.1021/jm060168g
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 2-氨基-5-氯-4-甲基苯磺酸 在 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-chloro-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methyl-benzenesulfonic acid
  参考文献：
  名称：

  Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site

  摘要：

  Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.

  DOI：

  10.1021/jm060168g

文献信息

• Sulfonamide derivatives to treat infection with hepatitis C virus
  申请人：Gopalsamy Ariamala

  公开号：US20070225344A1

  公开（公告）日：2007-09-27

  This invention is directed to compounds of formula (I): wherein R 1 , R 2 , X, and n are as defined herein, including all crystalline forms and pharmaceutically acceptable salts thereof, with the provisos that when X is CH 2 , n is 1, and R 1 is —COOH, then R 2 cannot be wherein A is CH 3 —, CH 3 CH 2 — or a haloalkyl of 1 to 2 carbon atoms, and B is a halogen; and when X is CH 2 , n is 2, and R 1 is —COOH, then R 2 cannot be The invention is also directed to compositions containing compounds of the invention and methods of using the compounds to treat or prevent hepatitis C virus infections.

  本发明涉及式(I)的化合物：其中R1、R2、X和n如本文所定义，包括所有晶体形式和其药学上可接受的盐，但有以下限制：当X为CH2，n为1，且R1为—COOH时，则R2不能为其中A为CH3—，CH3CH2—或1至2个碳原子的卤代烷基，B为卤素；当X为CH2，n为2，且R1为—COOH时，则R2不能为本发明还涉及含有该化合物的组合物以及使用该化合物治疗或预防丙型肝炎病毒感染的方法。
• WO2007/92558
  申请人：——

  公开号：——

  公开（公告）日：——
• SULFONAMIDE DERIVATIVES TO TREAT INFECTION WITH HEPATITIS C VIRUS
  申请人：Wyeth

  公开号：EP1981845A2

  公开（公告）日：2008-10-22
• [EN] SULFONAMIDE DERIVATIVES TO TREAT INFECTION WITH HEPATITIS C VIRUS<br/>[FR] DÉRIVÉS DE SULFONAMIDE UTILISÉS POUR TRAITER UNE INFECTION PAR LE VIRUS DE L'HÉPATITE C
  申请人：WYETH CORP

  公开号：WO2007092558A2

  公开（公告）日：2007-08-16

  [EN] This invention is directed to compounds of formula (I): wherein R₁, R₂, X, and n are as defined herein, including all crystalline forms and pharmaceutically acceptable salts thereof, with the provisos that when X is CH₂, n is 1, and R₁ is -COOH, then R₂ cannot be formula (A) wherein A is CH₃-, CH₃CH₂- or a haloalkyl of 1 to 2 carbon atoms, and B is a halogen; and when X is CH₂, n is 2, and R₁ is -COOH, then R₂ cannot be formula (A) or formula (B). The invention is also directed to compositions containing compounds of the invention and methods of using the compounds to treat or prevent hepatitis C virus infections.
  [FR] L'invention concerne des composés de formule (I), dans laquelle R₁, R₂, X et n sont tels que définis dans le mémorandum descriptif, y compris toutes le formes cristallines et sels pharmaceutiquement acceptables desdits composés, à condition que, quand X est CH₂, n est 1 et R₁ est -COOH, alors R₂ ne peut pas représenter la formule (A) dans laquelle A est CH₃-, CH₃CH₂- ou un haloalkyle de 1 à 2 atomes de carbone, et B un halogène; et quand X est CH₂, n est 2 et R₁ est -COOH, alors R₂ ne peut pas représenter la formule (A) ou la formule (B). L'invention concerne en outre des compositions contenant les composés de l'invention, et des méthodes d'utilisation des composés pour traiter ou prévenir des infections par le virus de l'hépatite C.
• Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site
  作者：Ariamala Gopalsamy、Rajiv Chopra、Kitae Lim、Gregory Ciszewski、Mengxiao Shi、Kevin J. Curran、Steven F. Sukits、Kristine Svenson、Joel Bard、John W. Ellingboe、Atul Agarwal、Girija Krishnamurthy、Anita Y. M. Howe、Mark Orlowski、Boris Feld、John O'Connell、Tarek S. Mansour

  DOI：10.1021/jm060168g

  日期：2006.6.1

  Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.