4'-cyano-biphenyl-4-sulfonic acid (6-methyl-pyridin-2-yl)-amide | 857289-84-0

• 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: 4'-cyano-biphenyl-4-sulfonic acid (6-methyl-pyridin-2-yl)-amide
• 英文别名: N-(Pyridin-2-yl) arylsulfonamide, 22；4-(4-cyanophenyl)-N-(6-methylpyridin-2-yl)benzenesulfonamide
• CAS: 857289-84-0
• 化学式: C₁₉H₁₅N₃O₂S
• 分子量: 349.413
• InChiKey: OWYWZVRZIUBCOM-UHFFFAOYSA-N

物化性质

• 沸点：
  558.2±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  91.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4'-cyano-biphenyl-4-sulfonic acid (6-methyl-pyridin-2-yl)-amide 在 sodium hydroxide 、 水 、 双氧水 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 4'-(6-Methyl-pyridin-2-ylsulfamoyl)-biphenyl-4-carboxylic acid amide
  参考文献：
  名称：

  Amino heterocyclyl inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1

  摘要：

  本发明涉及具有化学式(I)或其药学上可接受的盐的化合物：该发明还涉及包含化学式(I)或化学式(II)化合物的药物组合物，以及治疗通过调节11-β-hsd-1介导的疾病的方法，该方法包括向哺乳动物施用化学式(I)或化学式(II)化合物的有效量。

  公开号：

  US20050148631A1
• 作为产物：
  描述：

  4-氰基联苯 在 吡啶 、 氯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 4'-cyano-biphenyl-4-sulfonic acid (6-methyl-pyridin-2-yl)-amide
  参考文献：
  名称：

  N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1: Strategies to eliminate reactive metabolites

  摘要：

  N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1. A screen for bioactivation revealed that these compounds formed glutathione conjugates. This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors. Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11 beta-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.[GRAPHICS](C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.066

文献信息

• 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11BETA-HSD1) INHIBITORS AND USES THEREOF
  申请人：Jacobson Peer B.

  公开号：US20110159005A1

  公开（公告）日：2011-06-30

  A method for treating a patient suffering from inflammation, chronic inflammation, pain, rheumatoid arthritis (RA), osteoarthritis and osteoporosis, comprising administering an effective amount of a selective inhibitor of the 11-β-hydroxysteroid dehydrogenase Type 1 enzyme.
• US8871208B2
  申请人：——

  公开号：US8871208B2

  公开（公告）日：2014-10-28
• Amino heterocyclyl inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
  申请人：Cheng Hengmiao

  公开号：US20050148631A1

  公开（公告）日：2005-07-07

  The present invention relates to compounds with the formula (I), or a pharmaceutically acceptable salt thereof: The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) or formula (II) and methods of treating a condition that is mediated by the modulation of 11-β-hsd-1, the method comprising administering to a mammal an effective amount of a compound of formula (I) or formula (II).

  本发明涉及具有化学式(I)或其药学上可接受的盐的化合物：该发明还涉及包含化学式(I)或化学式(II)化合物的药物组合物，以及治疗通过调节11-β-hsd-1介导的疾病的方法，该方法包括向哺乳动物施用化学式(I)或化学式(II)化合物的有效量。
• N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1: Strategies to eliminate reactive metabolites
  作者：Sajiv K. Nair、Jean J. Matthews、Stephan J. Cripps、Hengmiao Cheng、Jacqui E. Hoffman、Christopher Smith、Stanley Kupchinsky、Michael Siu、Wendy D. Taylor、Yong Wang、Theodore O. Johnson、Klaus R. Dress、Martin P. Edwards、Sue Zhou、Natilie A. Hosea、Amy LaPaglia、Ping Kang、Arturo Castro、Jacques Ermolieff、Andrea Fanjul、Jennifer E. Vogel、Paul Rejto、Deepak Dalvie

  DOI：10.1016/j.bmcl.2013.02.066

  日期：2013.4

  N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1. A screen for bioactivation revealed that these compounds formed glutathione conjugates. This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors. Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11 beta-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.[GRAPHICS](C) 2013 Elsevier Ltd. All rights reserved.