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] HETEROCYCLIC INHIBITORS OF PCSK9<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE PCSK9
  申请人：CARDIO THERAPEUTICS PTY LTD

  公开号：WO2022133529A1

  公开（公告）日：2022-06-30

  This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I): (I) wherein R1, R2, R3and L are described herein.

  本申请涉及化合物，这些化合物可以作为PCSK9的抑制剂或以其他方式调节其活性，或其药物可接受的盐，溶剂化物，前药或多晶型，以及包含这些化合物的组合物和配方，以及使用和制备这些化合物的方法。其中化合物包括公式（I）的化合物：(I)，其中R1，R2，R3和L如本文所述。
• 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.