furo[2,3-c]pyridine-2-carboxylic acid 4-(4-oxetan-3-ylpiperazine-4-sulfonyl)benzylamide | 1453175-08-0

• 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: furo[2,3-c]pyridine-2-carboxylic acid 4-(4-oxetan-3-ylpiperazine-4-sulfonyl)benzylamide
• 英文别名: N-(4-((4-(oxetan-3-yl)piperazin-1-yl)sulfonyl)benzyl)furo-[2,3-c]pyridine-2-carboxamide；N-[[4-[4-(oxetan-3-yl)piperazin-1-yl]sulfonylphenyl]methyl]furo[2,3-c]pyridine-2-carboxamide
• CAS: 1453175-08-0
• 化学式: C₂₂H₂₄N₄O₅S
• 分子量: 456.522
• InChiKey: OGDYOHGOSNSDAE-UHFFFAOYSA-N

物化性质

• 密度：
  1.414±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(4-cyanobenzenesulfonyl)piperazine-1-carboxylic acid tert-butyl ester 在 titanium(IV) isopropylate 、 氨 、 氢气 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 furo[2,3-c]pyridine-2-carboxylic acid 4-(4-oxetan-3-ylpiperazine-4-sulfonyl)benzylamide
  参考文献：
  名称：

  Fragment-Based Identification of Amides Derived from trans-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

  摘要：

  Potent, trans-2-(pyridin-3-yl)cyclopropane-carboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, K-D = 51 mu M) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC50 = 0.0051 mu M, A2780 cell culture IC50 = 0.000 49 mu M) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model.

  DOI：

  10.1021/jm4015108

文献信息

• [EN] AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES<br/>[FR] DÉRIVÉS SULFOXYDES ET SULFONES AMIDO-BENZYLIQUES
  申请人：GENENTECH INC

  公开号：WO2013127266A1

  公开（公告）日：2013-09-06

  The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  这项发明涉及某些酰胺基苯甲基亚砜和砜化合物，包括这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。
• AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES
  申请人：Bair Kenneth W.

  公开号：US20150104384A1

  公开（公告）日：2015-04-16

  The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  本发明涉及某些酰胺基苯基亚砜和砜化合物，包括这些化合物的药物组合物和使用这些化合物的治疗方法。
• Amido-benzyl sulfone and sulfoxide derivates
  申请人：Forma TM, LLC

  公开号：US10696692B2

  公开（公告）日：2020-06-30

  The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  本发明涉及某些氨基苄基亚砜和砜化合物、包含此类化合物的药物组合物以及使用此类化合物进行治疗的方法。
• [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.