2-methyl-5-(piperidin-4-yloxy)pyridine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-methyl-5-(piperidin-4-yloxy)pyridine
• 英文别名: 6-Methyl-3-pyridinyl 4-piperidinyl ether；2-methyl-5-piperidin-4-yloxypyridine
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: IUYVQHKOIHBGRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-6-甲基喹唑啉 、 2-methyl-5-(piperidin-4-yloxy)pyridine 在 N-甲基吡咯烷酮 、 N,N-二异丙基乙胺 作用下， 反应 0.25h， 生成 6-Methyl-4-[4-(6-methylpyridin-3-yl)oxypiperidin-1-yl]quinazoline
  参考文献：
  名称：

  Discovery and optimization of a novel series of highly CNS penetrant M 4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3- d ]pyrimidine core

  摘要：

  This Letter describes the chemical optimization of a novel series of M-4 positive allosteric modulators (PAMs) based on a 5,6-dimethyl-4-(piperidin-1-yl) thieno[2,3-d]pyrimidine core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent and selective, but not CNS penetrant. Potency was maintained, while CNS penetration was improved (rat brain: plasma K-p = 0.74), within the original core after several rounds of optimization; however, the thieno[2,3-d]pyrimidine core was subject to extensive oxidative metabolism. Ultimately, we identified a 6-fluoroquinazoline core replacement that afforded good M-4 PAM potency, muscarinic receptor subtype selectivity and CNS penetration (rat brain:plasma K-p > 10). Moreover, this campaign provided fundamentally distinct M-4 PAM chemotypes, greatly expanding the available structural diversity for this exciting CNS target. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.05.010
• 作为产物：
  描述：

  N-Boc-4-羟基哌啶 在 偶氮二甲酸二异丙酯 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 3.33h， 生成 2-methyl-5-(piperidin-4-yloxy)pyridine
  参考文献：
  名称：

  [EN] OGA INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS D'OGA

  摘要：

  本发明涉及具有式(I)所示结构的O-GIcNAc水解酶（OGA）抑制剂。该发明还涉及包含这种化合物的药物组合物、制备这种化合物和组合物的方法，以及利用这种化合物和组合物预防和治疗抑制OGA有益的疾病，如tau病变，特别是阿尔茨海默病或进行性上核性麻痹；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化或额颞叶痴呆症。其中RB是从（b-1）到（b-6）组成的芳香杂双环基团。

  公开号：

  WO2019243530A1

文献信息

• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2019243530A1

  公开（公告）日：2019-12-26

  The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors having the structure shown in formula (I). The invention is also directed to pharmaceutical compositions comprising such compounds to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations. wherein RB is an aromatic heterobicyclic radical selected from the group consisting of (b-1) to (b-6).

  本发明涉及具有式(I)所示结构的O-GIcNAc水解酶（OGA）抑制剂。该发明还涉及包含这种化合物的药物组合物、制备这种化合物和组合物的方法，以及利用这种化合物和组合物预防和治疗抑制OGA有益的疾病，如tau病变，特别是阿尔茨海默病或进行性上核性麻痹；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化或额颞叶痴呆症。其中RB是从（b-1）到（b-6）组成的芳香杂双环基团。
• PYRIDO[3,4-d]PYRIMIDINE DERIVATIVE AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
  申请人：Teijin Pharma Limited

  公开号：EP3305785A1

  公开（公告）日：2018-04-11

  The purpose of the present invention is to provide a compound having an excellent CDK4/6 inhibiting activity. The present invention is a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof.

  本发明的目的是提供一种具有优异 CDK4/6 抑制活性的化合物。本发明是通式（I）代表的化合物或其药学上可接受的盐。
• HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF
  申请人：Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

  公开号：EP3929198A1

  公开（公告）日：2021-12-29

  The present invention relates to a heterocyclic compound, a pharmaceutical composition comprising same, a preparation method therefor, and a use thereof. Specifically, the compound of the present invention is represented by formula (I), and used for preventing or treating a disease or condition related to RET activity.

  本发明涉及一种杂环化合物、包含该化合物的药物组合物、其制备方法及其用途。具体而言，本发明的化合物由式（I）表示，用于预防或治疗与 RET 活性有关的疾病或病症。
• EP3929198
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core
  作者：Blake R. Bewley、Paul K. Spearing、Rebecca L. Weiner、Vincent B. Luscombe、Xiaoyan Zhan、Sichen Chang、Hyekyung P. Cho、Alice L. Rodriguez、Colleen M. Niswender、P. Jeffrey Conn、Thomas M. Bridges、Darren W. Engers、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2017.08.043

  日期：2017.9

  This Letter details the discovery and subsequent optimization of a novel M-4 PAM scaffold based on an 6fluoro-4-(piperidin-1-yl) quinoline-3-carbonitrile core, which represents a distinct departure from the classical M4 PAM chemotypes. Optimized compounds in this series demonstrated improved M-4 PAM potency on both human and rat M-4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain: plasma K-p = 5.3, K-p,K-uu = 2.4; MDCK-MDR1 (P-gp) ER = 1.1). (C) 2017 Elsevier Ltd. All rights reserved.