4-(2,6-二氯嘧啶-4-基)哌啶-1-羧酸叔丁酯 | 1439823-01-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(2,6-二氯嘧啶-4-基)哌啶-1-羧酸叔丁酯
• 英文名称: tert-butyl 4-(2,6-dichloropyrimidin-4-yl)piperidine-1-carboxylate
• CAS: 1439823-01-4
• 化学式: C₁₄H₁₉Cl₂N₃O₂
• 分子量: 332.23
• InChiKey: SMWIHIPPDLQJIX-UHFFFAOYSA-N

物化性质

• 沸点：
  433.4±45.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-(2,6-二氯嘧啶-4-基)哌啶-1-羧酸叔丁酯 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 (R)-6-(1-methylpiperidin-4-yl)-2-(2-methylpyrrolidin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)pyrimidin-4-amine
  参考文献：
  名称：

  [EN] C-LINKED HETEROCYCLOALKYL SUBSTITUTED PYRIMIDINES AND THEIR USES
  [FR] PYRIMIDINES À SUBSTITUTION HÉTÉROCYCLOALKYLE LIÉES À C ET LEURS UTILISATIONS

  摘要：

  本发明提供了式（I-I）的嘧啶化合物及其实施例。在式（I-I）中，R1、R2、R3、R4、R5、R6'、m、n和“het”环如本文所述。还提供了包含式（I）化合物的药物组合物以及使用这些化合物和组合物的方法。

  公开号：

  WO2014177524A1

文献信息

• C-Linked Heterocycloaklyl Substituted Pyrimidines and their uses
  申请人：Genentech, Inc.

  公开号：US20160046608A1

  公开（公告）日：2016-02-18

  The present invention provides for pyrimidine compounds of Formula I-I and embodiments thereof In Formula I-I in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , m, n and the “het” ring are as described herein. Also provided are pharmaceutical compositions comprising compounds of Formula I and methods of using such compounds and compositions.

  本发明提供了式I-I的嘧啶化合物及其具体实施例。式I-I中，R1、R2、R3、R4、R5、R6、m、n和“het”环如本文所述。还提供了包含式I化合物的药物组合物以及使用这些化合物和组合物的方法。
• BIHETEROARYL COMPOUNDS AND USES THEREOF
  申请人：Genentech, Inc.

  公开号：US20160052940A1

  公开（公告）日：2016-02-25

  The present invention provides for compounds of Formula I-I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R 1 , R 2 , R 3 , X 1 , X 2 , A and Cy variable in Formula I-I all have the meaning as defined herein.

  本发明提供了I-I式化合物及其衍生物和盐，用于治疗疾病（例如神经退行性疾病）。公式I-I中的R1、R2、R3、X1、X2、A和Cy变量均具有本文所定义的含义。
• Biheteroaryl compounds and uses thereof
  申请人：Genentech, Inc.

  公开号：US10010549B2

  公开（公告）日：2018-07-03

  The present invention provides for compounds of Formula I-I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R1, R2, R3, X1, X2, A and Cy variable in Formula I-I all have the meaning as defined herein.

  本发明提供了用于治疗疾病（如神经退行性疾病）的式-I-I化合物及其实施方案和盐。式-I-I中的R1、R2、R3、X1、X2、A和Cy变量均具有本文所定义的含义。
• Potassium channel modulators
  申请人：Cadent Therapeutics, Inc.

  公开号：US10774064B2

  公开（公告）日：2020-09-15

  Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions which can be affected by potassium channel modulation. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.

  本发明提供了式 (I) 的新型化合物：及其药学上可接受的盐类，它们可用于治疗各种可受钾通道调节影响的疾病、失调或病症。还提供了包含式（I）新型化合物及其药学上可接受的盐的药物组合物，以及将其用于治疗一种或多种与钾通道相关的疾病、失调或病症的方法。
• Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models
  作者：Snahel Patel、Frederick Cohen、Brian J. Dean、Kelly De La Torre、Gauri Deshmukh、Anthony A. Estrada、Arundhati Sengupta Ghosh、Paul Gibbons、Amy Gustafson、Malcolm P. Huestis、Claire E. Le Pichon、Han Lin、Wendy Liu、Xingrong Liu、Yichin Liu、Cuong Q. Ly、Joseph P. Lyssikatos、Changyou Ma、Kimberly Scearce-Levie、Young G. Shin、Hilda Solanoy、Kimberly L. Stark、Jian Wang、Bei Wang、Xianrui Zhao、Joseph W. Lewcock、Michael Siu

  DOI：10.1021/jm5013984

  日期：2015.1.8

  Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding mode and specific design parameters to optimize for CNS druglike molecules, we came to focus on the di(pyridin-2-yl)amines because of their combination of desirable potency and good brain penetration following oral dosing. Our lead inhibitor GNE-3511 (26) displayed concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. These results suggest that specific pharmacological inhibition of DLK may have therapeutic potential in multiple indications.