1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-ylpiperidine-1-sulfonyl)benzylamide | 1453175-13-7

• 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: 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-ylpiperidine-1-sulfonyl)benzylamide
• 英文别名: 1H-Pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-yl-piperidine-1-sulfonyl)-benzylamide；N-[[4-(4-pyrrolidin-1-ylpiperidin-1-yl)sulfonylphenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
• CAS: 1453175-13-7
• 化学式: C₂₃H₂₈N₆O₃S
• 分子量: 468.58
• InChiKey: RHOGMKTXIBDMGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-吡咯烷-1-基哌啶 在 氨 、 氢气 、 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 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-ylpiperidine-1-sulfonyl)benzylamide
  参考文献：
  名称：

  Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)

  摘要：

  Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.074
• 作为试剂：
  描述：

  4-{[(1H-pyrazolo[3_,4-b]pyridine-5-carbonyl)amino]methyl}benzenesulfonyl chloride 、 4-(pyrrolidin-1-yl)piperidine hydrochloride 、 三乙胺 在 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-ylpiperidine-1-sulfonyl)benzylamide 、 mobile phase A 、 水 、 mobile phase B 、 乙腈 、 N-[[3-(4-pyrrolidin-1-ylpiperidin-1-yl)sulfonylphenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 作用下， 以 二氯甲烷 为溶剂， 反应 25.24h， 以Isolation and concentration of the appropriate fractions afforded the title as a white solid (14.6 mg, 22%)的产率得到1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 4-(4-pyrrolidin-1-ylpiperidine-1-sulfonyl)benzylamide
  参考文献：
  名称：

  AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES

  摘要：

  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。

  公开号：

  US20150104384A1

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 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.
• Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
  作者：Xiaozhang Zheng、Kenneth W. Bair、Paul Bauer、Timm Baumeister、Krista K. Bowman、Alexandre J. Buckmelter、Maureen Caligiuri、Karl H. Clodfelter、Yezhen Feng、Bingsong Han、Yen-Ching Ho、Nikolai Kley、Hong Li、Xiaorong Liang、Bianca M. Liederer、Jian Lin、Justin Ly、Thomas O’Brien、Jason Oeh、Angela Oh、Dominic J. Reynolds、Deepak Sampath、Geeta Sharma、Nicholas Skelton、Chase C. Smith、Jarrod Tremayne、Leslie Wang、Weiru Wang、Zhongguo Wang、Hongxing Wu、Jiansheng Wu、Yang Xiao、Guangxing Yang、Po-wai Yuen、Mark Zak、Peter S. Dragovich

  DOI：10.1016/j.bmcl.2013.08.074

  日期：2013.10

  Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained. (C) 2013 Elsevier Ltd. All rights reserved.
• 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。