1H-吡唑并[3,4-b]吡啶-5-羧酸乙酯 | 1256824-48-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 中文名称: 1H-吡唑并[3,4-b]吡啶-5-羧酸乙酯
• 中文别名: 7-氮杂吲唑-5-羧酸乙酯
• 英文名称: Ethyl 1H-pyrazolo[3,4-B]pyridine-5-carboxylate
• CAS: 1256824-48-2
• 化学式: C₉H₉N₃O₂
• 分子量: 191.189
• InChiKey: DWBSMBXTDIFAGZ-UHFFFAOYSA-N

物化性质

• 沸点：
  345.3±22.0 °C(Predicted)
• 密度：
  1.339±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1H-吡唑并[3,4-b]吡啶-5-羧酸乙酯 在 水 、 sodium hydroxide 作用下， 反应 1.0h， 生成 1H-吡唑[3,4-b]嘧啶-5-羧酸
  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 、 氢气 、 三乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 1H-吡唑并[3,4-b]吡啶-5-羧酸乙酯
  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] BICYCLIC HETEROCYCLES AS MEK KINASE INHIBITORS<br/>[FR] HÉTÉROCYCLES BICYCLIQUES EN TANT QU'INHIBITEURS DE MEK KINASE
  申请人：GENENTECH INC

  公开号：WO2010003025A1

  公开（公告）日：2010-01-07

  The invention relates to bicyclic heterocycles of formulae I and II with anti-cancer and/or anti-inflammatory activity and more specifically with MEK kinase inhibitory activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth, treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  该发明涉及具有抗癌和/或抗炎活性的式I和式II的双环杂环化合物，更具体地具有MEK激酶抑制活性。该发明提供了用于抑制异常细胞生长、治疗过度增殖性疾病或治疗哺乳动物炎症性疾病的组合物和方法。该发明还涉及使用这些化合物进行体外、体内和体内诊断或治疗哺乳动物细胞或相关病理条件的方法。
• [EN] 1 -PHENOXY-3-(ALKYLAMINO)-PROPAN-2-OL DERIVATIVES AS CARM1 INHIBITORS AND USES THEREOF<br/>[FR] DÉRIVÉS DE 1-PHÉNOXY-3-(ALKYLAMINO)-PROPAN-2-OL EN TANT QU'INHIBITEURS DE CARM1 ET LEURS UTILISATIONS
  申请人：EPIZYME INC

  公开号：WO2014144455A1

  公开（公告）日：2014-09-18

  Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is an optionally substituted 6,5-bicyclic heteroaryl ring system comprising 2 to 5 nitrogen atoms, inclusive, wherein the point of attachment is provided on the 6-membered ring of the 6,5-bicyclic heteroaryl ring system, and wherein the 6-membered ring is further substituted with a group of formula -L1 -R3, wherein L1 and R3 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

  本文提供了Formula (I)的化合物及其药学上可接受的盐，以及药物组合物；其中X、R1、R2a、R2b、R2c、R2d的定义如本文所述，Ring HET是一个可选取代的含2到5个氮原子的6,5-双环杂芳基环系统，其中连接点位于6,5-双环杂芳基环系统的6个环上，并且6个环还进一步取代为一个具有式-L1-R3的基团，其中L1和R3的定义如本文所述。本发明的化合物对于抑制CARM1活性是有用的。还描述了利用这些化合物治疗CARM1介导的疾病的方法。
• [EN] CARM1 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE CARM1 ET LEURS UTILISATIONS
  申请人：EPIZYME INC

  公开号：WO2016044650A1

  公开（公告）日：2016-03-24

  Provided herein are compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is an optionally substituted 6,5-bicyclic heteroaryl ring system comprising 2 to 5 nitrogen atoms, inclusive, wherein the point of attachment is provided on the 6-membered ring of the 6,5-bicyclic heteroaryl ring system, and wherein the 6-membered ring is further substituted with a group of formula -L1-R3, wherein L1 and R3 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

  本文提供了化合物的结构式（I）：（I）及其药学上可接受的盐，以及其制剂；其中X，R1，R2a，R2b，R2c，R2d如本文所定义，环HET是一个可选择取代的含有2至5个氮原子的6,5-双环杂芳基环系统，其中连接点位于6,5-双环杂芳基环系统的6-环上，并且6-环进一步取代为一个具有式-L1-R3的基团，其中L1和R3如本文所定义。本发明的化合物对抑制CARM1活性是有用的。还描述了使用这些化合物治疗CARM1介导的疾病的方法。
• BICYCLIC HETEROCYCLES AS MEK KINASE INHIBITORS
  申请人：Genentech, Inc.

  公开号：EP2310373A1

  公开（公告）日：2011-04-20
• PYRAZOLO[3,4-B] PYRIDINE COMPOUNDS, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1737857A1

  公开（公告）日：2007-01-03