N-(6-氨基-2-吡啶基)-4'-氰基-[1,1'-联苯]-4-磺酰胺 | 857290-04-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(6-氨基-2-吡啶基)-4'-氰基-[1,1'-联苯]-4-磺酰胺
• 中文别名: 85729-4-1
• 英文名称: PF-915275
• 英文别名: N-(6-aminopyridin-2-yl)-4'-cyanobiphenyl-4-sulfonamide；N-(6-aminopyridin-2-yl)-4-(4-cyanophenyl)benzenesulfonamide
• CAS: 857290-04-1
• 化学式: C₁₈H₁₄N₄O₂S
• 分子量: 350.401
• InChiKey: ZESFDAKNYJQYKO-UHFFFAOYSA-N

物化性质

• 沸点：
  610.9±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  N-(6-氨基-2-吡啶基)-4'-氰基-[1,1'-联苯]-4-磺酰胺 、 乙醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 6.5h， 以63%的产率得到4'-cyano-N-[6-(ethylamino)pyridin-2-yl]biphenyl-4-sulfonamide
  参考文献：
  名称：

  WO2006/134467

  摘要：

  公开号：
• 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 N-(6-氨基-2-吡啶基)-4'-氰基-[1,1'-联苯]-4-磺酰胺
  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

• N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275
  作者：Michael Siu、Theodore O. Johnson、Yong Wang、Sajiv K. Nair、Wendy D. Taylor、Stephan J. Cripps、Jean J. Matthews、Martin P. Edwards、Thomas A. Pauly、Jacques Ermolieff、Arturo Castro、Natilie A. Hosea、Amy LaPaglia、Andrea N. Fanjul、Jennifer E. Vogel

  DOI：10.1016/j.bmcl.2009.05.011

  日期：2009.7

  N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with

  N-（吡啶-2-基）芳基磺酰胺被鉴定为11β-羟基类固醇脱氢酶1（11βHSD1）的抑制剂，该酶催化糖皮质激素可的松还原为皮质醇。糖皮质激素的调节异常与糖尿病和代谢综合征的发病机理有关。在这封信中，我们介绍了使用缺失策略开发具有改进的理化性质的有效配体的初步方法。该策略允许进一步优化效能，从而导致临床候选药物PF-915275的发现。
• 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).

  本发明涉及公式（I）的化合物或其药学上可接受的盐：本发明还涉及包含公式（I）或公式（II）的化合物的制药组合物以及治疗介导11-β-hsd-1调节的疾病的方法，该方法包括向哺乳动物投与公式（I）或公式（II）的化合物的有效量。
• N-(pyridin-2-yl)-sulfonamide derivatives
  申请人：Nair Sajiv Krishnan

  公开号：US20070072914A1

  公开（公告）日：2007-03-29

  The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds described herein, their pharmaceutically acceptable salts, hydrates and solvates, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11βHSD1).

  本发明涉及新型化合物，包括所述化合物的制药组合物，其药学上可接受的盐，水合物和溶剂化合物，以及化合物在医学上的应用和用于制备对人类11-β-羟基类固醇脱氢酶1型酶（11βHSD1）起作用的药物。
• HSD11B1 INHIBITORS FOR USE IN IMMUNOTHERAPY AND USES THEREOF
  申请人：UNIVERSITE DE GENEVE

  公开号：EP3878446A1

  公开（公告）日：2021-09-15

  The present invention relates to HSD11B1 inhibitors useful for increasing anti-tumor immune response in combination with immunotherapy, in particular for the treatment of cancers and to related compositions and methods using those.

  本发明涉及 HSD11B1 抑制剂，该抑制剂与免疫疗法结合使用可提高抗肿瘤免疫反应，特别是用于治疗癌症，本发明还涉及相关组合物和使用这些组合物的方法。
• Methods and compositions for treating alcohol use disorders
  申请人：Sanna Pietro Paolo

  公开号：US10039772B2

  公开（公告）日：2018-08-07

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.

  本发明公开了通过向患者施用 11β-羟基类固醇脱氢酶（11β-HSD）抑制剂以调节糖皮质激素作用来治疗酒精依赖症的方法和组合物。其中一种化合物是 11β-HSD 抑制剂卡本诺酮（18β-甘草次酸 3β-O-hemisuccinate ），临床上已广泛用于治疗胃炎和消化性溃疡。卡贝诺酮对 11β-HSD1 和 2 同工酶均有活性。令人惊讶的是，羧甲诺龙在大鼠和小鼠体内可减少基线饮酒量和过量饮酒量。申请人发现，羧诺龙的非对映异构体 18α-甘草次酸 3β-O-hemisuccinate (αCBX)对 11β-HSD2 具有选择性，也能有效减少小鼠的饮酒量。因此，11β-HSD 抑制剂是一类新的候选酗酒药物，现有的 11β-HSD 抑制剂药物可重新用于酗酒治疗。