[5-(3,5-Difluorophenyl)sulfonylpyridin-2-yl]methanamine

• 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: [5-(3,5-Difluorophenyl)sulfonylpyridin-2-yl]methanamine
• 英文别名: [5-(3,5-difluorophenyl)sulfonylpyridin-2-yl]methanamine
• 化学式: C₁₂H₁₀F₂N₂O₂S
• 分子量: 284.286
• InChiKey: AIEYTBUDTWNNSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [5-(3,5-Difluorophenyl)sulfonylpyridin-2-yl]methanamine 、 呋喃并[2,3-c]吡啶-2-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 furo[2,3-c]pyridin-2-carboxylic acid [5-(3,5-difluorobenzenesulfonyl)pyridin-2-ylmethyl]amide
  参考文献：
  名称：

  Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility

  摘要：

  Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD(7.4) was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.026
• 作为产物：
  描述：

  3,5-二氟苯硫酚 在 potassium carbonate 、 一水合肼 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.67h， 生成 [5-(3,5-Difluorophenyl)sulfonylpyridin-2-yl]methanamine
  参考文献：
  名称：

  Identification of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with no evidence of CYP3A4 time-dependent inhibition and improved aqueous solubility

  摘要：

  Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as the likely source of the TDI signal, and replacement with other bicyclic systems was found to reduce or eliminate the TDI finding. A strategy of reducing the number of aromatic rings and/or lowering cLogD(7.4) was then employed to significantly improve aqueous solubility. These efforts culminated in the discovery of 42, a compound with no evidence of TDI, improved aqueous solubility, and robust efficacy in tumor xenograft studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.026

文献信息

• PYRIDINYL AND PYRIMIDINYL SULFOXIDE AND SULFONE DERIVATIVES
  申请人：Bair Kenneth W

  公开号：US20150175621A1

  公开（公告）日：2015-06-25

  Disclosed are certain pyridinyl and pyrimidinyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds and methods of treatment using such compounds.

  本发明涉及某些吡啶基和嘧啶基亚砜和磺酰化合物、包含这些化合物的制药组合物以及使用这些化合物的治疗方法。
• US9458172B2
  申请人：——

  公开号：US9458172B2

  公开（公告）日：2016-10-04
• [EN] METHODS OF USING ANTAGONISTS OF NAD BIOSYNTHESIS FROM NICOTINAMIDE<br/>[FR] PROCÉDÉS D'UTILISATION D'ANTAGONISTES DE BIOSYNTHÈSE DE NICOTINAMIDE ADÉNINE DINUCLÉOTIDE À PARTIR DE NICOTINAMIDE
  申请人：GENENTECH INC

  公开号：WO2013170191A1

  公开（公告）日：2013-11-14

  Provided herein are NAD biosynthesis from nicotinamide antagonists (e.g., Nampt antagonists and/or NMNAT antagonists) and methods of using the same.