6-(3-chloro-4-fluorobenzoyl)-2-cyano-1-oxa-6-azaspiro[2.5]octane | 448920-97-6

• 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: 6-(3-chloro-4-fluorobenzoyl)-2-cyano-1-oxa-6-azaspiro[2.5]octane
• 英文别名: 6-[(3-chloro-4-fluorophenyl)carbonyl]-1-oxa-6-azaspiro[2.5]octane-2-carbonitrile；6-(3-chloro-4-fluorobenzoyl)-1-oxa-6-azaspiro[2.5]octane-2-carbonitrile
• CAS: 448920-97-6
• 化学式: C₁₄H₁₂ClFN₂O₂
• 分子量: 294.713
• InChiKey: MOKQWCBSDJFHJI-UHFFFAOYSA-N

物化性质

• 沸点：
  523.2±50.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  存放于室温、密封且干燥的环境中。

反应信息

• 作为反应物：
  描述：

  6-(3-chloro-4-fluorobenzoyl)-2-cyano-1-oxa-6-azaspiro[2.5]octane 以85的产率得到[1-(3-氯-4-氟苯甲酰基)-4-氟哌啶-4-基](氰基)甲醇
  参考文献：
  名称：

  Deuterium-Substituted Pyridin- And Pyrimidin-2-yl-Methylamine Compounds

  摘要：

  描述了结构式(I)的氘代吡啶和嘧啶-2-基甲胺化合物，它们是5-羟色胺受体激动剂。还描述了包含这些氘代吡啶和嘧啶-2-基甲胺化合物的药物组合物，以及使用它们的方法。

  公开号：

  US20180079742A1
• 作为产物：
  描述：

  N-(3-氯-4-氟苯甲酰基)-哌啶-4-酮 以48的产率得到6-(3-chloro-4-fluorobenzoyl)-2-cyano-1-oxa-6-azaspiro[2.5]octane
  参考文献：
  名称：

  Deuterium-Substituted Pyridin- And Pyrimidin-2-yl-Methylamine Compounds

  摘要：

  描述了结构式(I)的氘代吡啶和嘧啶-2-基甲胺化合物，它们是5-羟色胺受体激动剂。还描述了包含这些氘代吡啶和嘧啶-2-基甲胺化合物的药物组合物，以及使用它们的方法。

  公开号：

  US20180079742A1

文献信息

• Synthesis method and intermediates of pyridin-2-yl-methylamine
  申请人：——

  公开号：US20040116705A1

  公开（公告）日：2004-06-17

  The invention concerns a novel method for preparing pyridin-2-yl-methylamine derivatives by reducing amination of cyanohydrins.

  这项发明涉及一种通过还原氰醇胺化来制备吡啶-2-基甲胺衍生物的新方法。
• [EN] SYNTHESIS METHOD AND INTERMEDIATES OF PYRIDIN-2-YL-METHYLAMINE<br/>[FR] PROCEDE DE SYNTHESE ET INTERMEDIAIRES DE PYRIDIN-2-YL-METHYLAMINE
  申请人：PF MEDICAMENT

  公开号：WO2002064585A1

  公开（公告）日：2002-08-22

  La présente invention concerne un nouveau procédé de préparation de dérivés de la pyridin-2-yl-méthylamine par animation réductrice de cyanohydrines

  本发明涉及一种通过氰醇的还原动力学制备吡啶-2-基甲胺衍生物的新方法。
• Compounds for treating disorders sensitive to serotoninergic regulation controlled by the 5-HT1A receptors
  申请人：NEUROLIXIS

  公开号：US10562853B2

  公开（公告）日：2020-02-18

  The invention concerns compounds that possess a high affinity at 5-HT1A receptors and an agonist efficacy, as measured by Emax values from a cellular activation assay, that is higher than that of the compounds described in prior art. The capacity of the compounds of the invention to activate an effector protein complex is higher than that the most efficacious agonist described in prior art. Compounds of the invention also exhibit an exceptionally high selectivity (Ki ratio greater than 1000-fold) with respect, in particular, to dopamine D2 receptors and adrenergic receptors of the alpha1 subtype. This selectivity which constitutes a great advantage since it means that the compounds will avoid inducing (central and peripheral) effects associated with activating or inhibiting such receptors.

  本发明所涉及的化合物对 5-HT1A 受体具有高亲和力，并且根据细胞活化实验的 Emax 值衡量，其激动剂功效高于现有技术中所述的化合物。本发明化合物激活效应蛋白复合物的能力高于现有技术中最有效的激动剂。本发明的化合物还具有极高的选择性（Ki 比值大于 1000 倍），特别是对多巴胺 D2 受体和α1 亚型肾上腺素能受体。这种选择性具有很大的优势，因为它意味着本发明的化合物可以避免引起与激活或抑制这些受体相关的（中枢和外周）效应。
• Deuterium-substituted pyridin- and pyrimidin-2-yl-methylamine compounds
  申请人：Auspex Pharmaceuticals, Inc.

  公开号：US10626105B2

  公开（公告）日：2020-04-21

  Described are deuterium-substituted pyridin- and pyrimidin-2-yl-methylamine compounds of structural Formula (I), which are agonists of 5-hydroxytryptamine receptors. Also described are pharmaceutical compositions comprising the deuterium-substituted pyridin- and pyrimidin-2-yl-methylamine compounds, and methods of use thereof.

  描述了结构式（I）的氘代吡啶-和嘧啶-2-基-甲胺化合物，它们是 5-羟色胺受体的激动剂。还描述了包含氘代吡啶和嘧啶-2-基甲胺化合物的药物组合物及其使用方法。
• Novel Aryloxyethyl Derivatives of 1-(1-Benzoylpiperidin-4-yl)methanamine as the Extracellular Regulated Kinases 1/2 (ERK1/2) Phosphorylation-Preferring Serotonin 5-HT_1A Receptor-Biased Agonists with Robust Antidepressant-like Activity
  作者：Joanna Sniecikowska、Monika Gluch-Lutwin、Adam Bucki、Anna Więckowska、Agata Siwek、Magdalena Jastrzebska-Wiesek、Anna Partyka、Daria Wilczyńska、Karolina Pytka、Krzysztof Pociecha、Agnieszka Cios、Elżbieta Wyska、Anna Wesołowska、Maciej Pawłowski、Mark A. Varney、Adrian Newman-Tancredi、Marcin Kolaczkowski

  DOI：10.1021/acs.jmedchem.9b00062

  日期：2019.3.14

  Novel 1-(1-benzoylpiperidin-4-yl)methanamine derivatives were designed as "biased agonists" of serotonin 5-HT1A receptors. The compounds were tested in signal transduction assays (ERK1/2 phosphorylation, CAMP inhibition, Ca2+ mobilization, and beta-arrestin recruitment) which identified ERK1/2 phosphorylation-preferring aryloxyethyl derivatives. The novel series showed high 5-HT1A receptor affinity, >1000-fold selectivity versus noradrenergic alpha(1), dopamine D-2, serotonin 5-HT2A, histamine H-1, and muscarinic M-1 receptors, and favorable druglike properties (CNS-MPO, Fsp(3), LELP). The lead structure, (3-chloro-4-fluorophenyl) ( 4-fluor-4-(((2-(pyridin-2-yloxy)ethyl)amino)methyl)piperidin-1-yl)methanone (17, NLX-204), displayed high selectivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein. Preliminary in vivo studies confirmed its promising pharmacokinetic profile. 17 also robustly stimulated ERK1/2 phosphorylation in rat cortex and showed highly potent (MED = 0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test. These data suggest that the present 5-HT1A receptor-biased agonists could constitute promising antidepressant drug candidates.