(5S)-4-[(4-甲氧基苯基)甲基]-5-甲基吗啉-3-酮 | 169297-84-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: (5S)-4-[(4-甲氧基苯基)甲基]-5-甲基吗啉-3-酮
• 英文名称: (S)-5-methyl-4-(4-methoxybenzyl)morpholin-3-one
• 英文别名: (S)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one；(5S)-4-(4-Methoxybenzyl)-5-methyl-3-morpholinone；(5S)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one；(5S)-4-[(4-methoxyphenyl)methyl]-5-methylmorpholin-3-one
• CAS: 169297-84-1
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: DCCPSNCYDOCXEW-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5S)-4-[(4-甲氧基苯基)甲基]-5-甲基吗啉-3-酮 在 锂硼氢 、 三甲基氯硅烷 、 1-氯乙基氯甲酸酯 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 8.0h， 生成 (S)-3-甲基吗啉盐酸盐
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005
• 作为产物：
  描述：

  (S)-2-((4-methoxybenzyl)amino)propan-1-ol 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (5S)-4-[(4-甲氧基苯基)甲基]-5-甲基吗啉-3-酮
  参考文献：
  名称：

  Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer’s disease

  摘要：

  We herein describe the results of further evolution of GSK-3 beta inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3 beta inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.005

文献信息

• 3-(Imidazolyl)-2-alkoxypropanoic acids
  申请人：Pfizer Inc.

  公开号：US20030199522A1

  公开（公告）日：2003-10-23

  Compounds according to formula (I) wherein n is 0-3, R 1 is optionally substituted C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each independently selected from hydrogen and optionally substituted C 1-6 alkyl, or R 5 and R 8 are an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition. 1

  根据公式（I）中的化合物，其中n为0-3，R1为可选择的取代C1-6烷基，C2-6烯基或C2-6炔基，杂环，芳香杂环，芳基或氢，而R2、R3、R4、R5、R6、R7、R8和R9分别独立选择自氢和可选择取代的C1-6烷基，或R5和R8为烷基链，是新颖的。它们在治疗与纤维蛋白沉积相关的血栓性疾病和其他病理条件中具有用途。
• Stereoselective synthesis of novel methylene ether dipeptide isosteres
  作者：Bryan H. Norman、Julian S. Kroin

  DOI：10.1016/0040-4039(95)00712-l

  日期：1995.6

  We have developed a versatile new synthesis of the Ψ[CH2O] pseudopeptides from N-protected 5-substituted morpholin-3-ones. This approach focuses on a stereoselective alkylation of the morpholin-3-ones. The resulting alkylation products were used in the synthesis of some previously unavailable Ψ[CH2O] dipeptides.

  我们已经开发了一种由N保护的5-取代的吗啉-3-酮合成Ψ[CH 2 O]假肽的通用新方法。该方法集中于吗啉-3-酮的立体选择性烷基化。所得的烷基化产物用于合成某些先前无法获得的Ψ[CH 2 O]二肽。
• 3-(imidazolyl)-2-alkoxypropanoic acids
  申请人：Pfizer Inc.

  公开号：US20040254164A1

  公开（公告）日：2004-12-16

  Compounds according to formula (I) wherein n is 0-3, R′ is optionally substituted C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each independently selected from hydrogen and optionally substituted C 1-6 alkyl, or R 5 and R 8 are an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition. 1

  化学式为（I）的化合物中，n为0-3，R′为可选取代的C1-6烷基，C2-6烯基或C2-6炔基，杂环，芳香杂环，芳基或氢，而R2，R3，R4，R5，R6，R7，R8和R9各自独立地选择氢和可选取代的C1-6烷基，或者R5和R8是一个烷基链，这些化合物是新颖的。它们在治疗与纤维蛋白沉积相关的血栓性疾病和其他病理情况中有用。
• INHIBITORS OF JANUS KINASES
  申请人：Altman Michael

  公开号：US20100256097A1

  公开（公告）日：2010-10-07

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了一种抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这些抑制剂化合物的组合物和通过向需要治疗骨髓增生性疾病或癌症的患者施用该化合物来抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。
• Inhibitors of janus kinases
  申请人：Altman Michael

  公开号：US08367706B2

  公开（公告）日：2013-02-05

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了抑制四种已知哺乳动物JAK激酶（JAK1，JAK2，JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这些抑制剂化合物的组合物以及通过向需要治疗骨髓增生性疾病或癌症的患者施用该化合物来抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。