4-甲氧基-4-哌啶甲醇 | 1082040-31-0

• 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-甲氧基-4-哌啶甲醇
• 英文名称: (4-methoxypiperidin-4-yl)methanol
• CAS: 1082040-31-0
• 化学式: C₇H₁₅NO₂
• mdl: MFCD11845426
• 分子量: 145.202
• InChiKey: DPBSQLYPDQHIBL-UHFFFAOYSA-N

物化性质

• 沸点：
  224℃
• 密度：
  1.05
• 闪点：
  90℃

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲氧基-4-哌啶甲醇 在 草酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 ethyl 4-methoxy-4-[[(3S)-3-(2-oxo-3H-indol-1-yl)pyrrolidin-1-yl]methyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of NovelN-Substituted Oxindoles as Selective M₁and M₄Muscarinic Acetylcholine Receptors Partial Agonists

  摘要：

  Activation of the M-1 and M-4 muscarinic acetylcholine receptors is thought to play an important role in improving the symptoms of schizophrenia. However, discovery of selective agonists for these receptors has been a challenge, considering the high sequence homology and conservation of the orthosteric acetylcholine binding site among muscarinic acetylcholine receptor subtypes. We report in this study the discovery of novel N-substituted oxindoles as potent muscarinic acetylcholine receptor partial agonists selective for M-1 and M-4 over M-2, M-3, and M-5. Among these oxindoles, compound 1 showed high selectivity for the M-1 and M-4 receptors with remarkable penetration into the central nervous system. Compound 1 reversed methamphetamine- and apomorphine-induced psychosis-like behaviors with low potency to extrapyramidical and peripheral side effects.

  DOI：

  10.1021/ml300372f
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 lithium aluminium tetrahydride 、 正丁基锂 、 sodium hydride 、 二异丙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 36.0h， 生成 4-甲氧基-4-哌啶甲醇
  参考文献：
  名称：

  Discovery of NovelN-Substituted Oxindoles as Selective M₁and M₄Muscarinic Acetylcholine Receptors Partial Agonists

  摘要：

  Activation of the M-1 and M-4 muscarinic acetylcholine receptors is thought to play an important role in improving the symptoms of schizophrenia. However, discovery of selective agonists for these receptors has been a challenge, considering the high sequence homology and conservation of the orthosteric acetylcholine binding site among muscarinic acetylcholine receptor subtypes. We report in this study the discovery of novel N-substituted oxindoles as potent muscarinic acetylcholine receptor partial agonists selective for M-1 and M-4 over M-2, M-3, and M-5. Among these oxindoles, compound 1 showed high selectivity for the M-1 and M-4 receptors with remarkable penetration into the central nervous system. Compound 1 reversed methamphetamine- and apomorphine-induced psychosis-like behaviors with low potency to extrapyramidical and peripheral side effects.

  DOI：

  10.1021/ml300372f

文献信息

• [EN] INHIBITORS OF MUTANT FORMS OF EGFR<br/>[FR] INHIBITEURS DE FORMES MUTANTES DE L'EGFR
  申请人：BLUEPRINT MEDICINES CORP

  公开号：WO2021133809A1

  公开（公告）日：2021-07-01

  The present disclosure provides a compound represented by structural formula (I) : or a pharmaceutically acceptable salt thereof useful for treating a cancer.

  本公开提供了一种由结构公式（I）表示的化合物：或其药用可接受的盐，用于治疗癌症。
• [EN] AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF T790M CONTAINING EGFR MUTANTS<br/>[FR] COMPOSÉS AMINOPYRIMIDINES EN TANT QU'INHIBITEURS DE MUTANTS D'EGFR CONTENANT T790M
  申请人：GENENTECH INC

  公开号：WO2014081718A1

  公开（公告）日：2014-05-30

  This invention relates to novel compounds of formula (I) which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer. (Formula I)

  这项发明涉及公式（I）的新化合物，这些化合物是T790M含有EGFR突变体的抑制剂，涉及含有它们的药物组合物，它们的制备方法，以及它们在预防或治疗癌症中的应用。
• HPK1 ANTAGONISTS AND USES THEREOF
  申请人：Nimbus Saturn, Inc.

  公开号：US20210078996A1

  公开（公告）日：2021-03-18

  The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.

  本发明提供了化合物、其组合物以及使用这些化合物用于抑制HPK1和治疗HPK1介导的疾病的方法。
• Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study
  作者：Robert Heald、Krista K. Bowman、Marian C. Bryan、Daniel Burdick、Bryan Chan、Emily Chan、Yuan Chen、Saundra Clausen、Belen Dominguez-Fernandez、Charles Eigenbrot、Richard Elliott、Emily J. Hanan、Philip Jackson、Jamie Knight、Hank La、Michael Lainchbury、Shiva Malek、Sam Mann、Mark Merchant、Kyle Mortara、Hans Purkey、Gabriele Schaefer、Stephen Schmidt、Eileen Seward、Steve Sideris、Lily Shao、Shumei Wang、Kuen Yeap、Ivana Yen、Christine Yu、Timothy P. Heffron

  DOI：10.1021/acs.jmedchem.5b01412

  日期：2015.11.25

  Because of their increased activity against activating mutants, first-generation epidermal growth factor receptor (EGFR) kinase inhibitors have had remarkable success in treating non-small-cell lung cancer (NSCLC) patients, but acquired resistance, through a secondary mutation of the gatekeeper residue, means that clinical responses only last for 8–14 months. Addressing this unmet medical need requires

  由于第一代表皮生长因子受体（EGFR）激酶抑制剂具有增强的针对激活突变体的活性，因此在治疗非小细胞肺癌（NSCLC）患者方面取得了显著成功，但通过关守的二次突变获得了耐药性残留，意味着临床反应仅持续8-14个月。为了满足这种未满足的医疗需求，需要能够同时靶向两种最常见的双突变体的药物：T790M / L858R（TMLR）和T790M / del（746-750）（TMdel）。在本文中，我们描述了如何使用侧重于结构指导的效价增加而不增加亲脂性或降低三维特征的策略优化非共价双突变体选择性先导化合物。经过连续几轮设计和合成，发现通过与酶的直接相互作用和/或对近端配体氧原子的影响，在4-羟基-和4-甲氧基哌啶基上进行顺式氟取代可提供协同，大量和特定的效能增强。氟羟基哌啶系列的进一步发展导致鉴定了一对非对映异构体，这些非对映异构体在体外显示出对T790M突变体比野生型EGFR（wtEGFR）具有
• [EN] METALLO-BETA-LACTAMASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASE ET LEURS MÉTHODES D'UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2019018186A1

  公开（公告）日：2019-01-24

  The present invention relates to metallo-β-lactamase inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

  本发明涉及具有以下结构的金属β-内酰胺酶抑制剂化合物的药物学可接受的盐，其中Z、RA、X1、X2和R1如本文所定义。本发明还涉及包含本发明的金属β-内酰胺酶抑制剂化合物或其药学上可接受的盐以及药学上可接受的载体的组合物，可选地与β-内酰胺类抗生素和/或β-内酰胺酶抑制剂结合。该发明还涉及治疗细菌感染的方法，包括向患者投予本发明化合物的治疗有效量，结合治疗有效量的一种或多种β-内酰胺类抗生素，可选地结合一种或多种β-内酰胺酶抑制剂化合物。本发明的化合物在克服抗生素耐药性的方法中具有用处。