tert-butyl 3-(2,6-dichloropyrimidin-4-yl)piperidine-1-carboxylate | 1636884-12-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 3-(2,6-dichloropyrimidin-4-yl)piperidine-1-carboxylate
• CAS: 1636884-12-2
• 化学式: C₁₄H₁₉Cl₂N₃O₂
• 分子量: 332.23
• InChiKey: ASMZMGLKODDNNR-UHFFFAOYSA-N

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

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2,6-dichloropyrimidin-4-yl)piperidine-1-carboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 N,N-二异丙基乙胺 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models

  摘要：

  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.

  DOI：

  10.1021/jm5013984
• 作为产物：
  描述：

  tert-butyl 3-(2,6-dihydroxypyrimidin-4-yl)piperidine-1-carboxylate 在 三氯氧磷 作用下， 反应 3.0h， 生成 tert-butyl 3-(2,6-dichloropyrimidin-4-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models

  摘要：

  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.

  DOI：

  10.1021/jm5013984

文献信息

• [EN] C-LINKED HETEROCYCLOALKYL SUBSTITUTED PYRIMIDINES AND THEIR USES<br/>[FR] PYRIMIDINES À SUBSTITUTION HÉTÉROCYCLOALKYLE LIÉES À C ET LEURS UTILISATIONS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014177524A1

  公开（公告）日：2014-11-06

  The present invention provides for pyrimidine compounds of Formula (I-I) and embodiments thereof. In Formula (I-I) in which R1, R2, R3, R4, R5, R6' 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。
• 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。
• US9868720B2
  申请人：——

  公开号：US9868720B2

  公开（公告）日：2018-01-16