N-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide | 1362132-18-0

• 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: N-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
• 英文别名: N-[(4-piperidin-1-ylsulfonylphenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
• CAS: 1362132-18-0
• 化学式: C₁₉H₂₁N₅O₃S
• 分子量: 399.473
• InChiKey: VMSFYJMVYXMVAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟基-1-[(4-甲氧基苯基)甲基]-1H-吡唑并[3,4-b]吡啶-5-羧酸乙酯 在 10 wt% Pd(OH)2 on carbon 、 水 、 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 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
  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

文献信息

• [EN] NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS POUR L'INHIBITION DE NAMPT
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2012031197A1

  公开（公告）日：2012-03-08

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，以及它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示：
• NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
  申请人：Bair Kenneth W.

  公开号：US20140294805A1

  公开（公告）日：2014-10-02

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，其合成，应用和解毒剂。本发明的一个示例化合物如下所示：
• 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。
• Compounds and compositions for the inhibition of NAMPT
  申请人：Forma TM, LLC

  公开号：US10272072B2

  公开（公告）日：2019-04-30

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及抑制 NAMPT 的化合物和组合物、其合成、应用和解毒剂。本发明的一种说明性化合物如下所示：
• 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。