(S)-2-[2-(4-Methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one | 503860-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (S)-2-[2-(4-Methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one
• 英文别名: 2-[(2S)-2-(4-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one
• CAS: 503860-55-7
• 化学式: C₂₀H₂₁N₅O₃
• 分子量: 379.418
• InChiKey: RNVKAFMBGLDRGV-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氧代-3-(嘧啶-4-基)-丙酸乙酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成 (S)-2-[2-(4-Methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one
  参考文献：
  名称：

  2-（2-苯基吗啉-4-基）嘧啶-4（3 H）-ones; 一类新型的有效，选择性和口服活性糖原合酶激酶3β抑制剂

  摘要：

  合成了一系列2-（2-苯基吗啉-4-基）嘧啶-4（3 H）-酮，并检查了它们对糖原合酶激酶-3β（GSK-3β）的抑制活性。我们发现21，29和30，以在体外具有GSK-3β在体外PK性能良好的抑制活性有效。21显示在小鼠口服后tau磷酸化显着降低，PK表现出色。

  DOI：

  10.1016/j.bmcl.2013.09.020

文献信息

• 3-Substituted-4-pyrimidone derivatives
  申请人：Uehara Fumiaki

  公开号：US20050130967A1

  公开（公告）日：2005-06-16

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof having inhibitory activity against tau protein kinase 1: wherein R 1 represents a C 1 -C 12 alkyl group which may be substituted; R represents, for example, a group represented by the following formula (II): wherein R2 and R 3 independently represent a hydrogen atom or a C 1 -C 8 alkyl group; R 4 represents a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.

  一种由式(I)表示的吡啶酮衍生物或其盐，或其溶剂化物或水合物，具有对tau蛋白激酶1的抑制活性：其中，R1代表可取代的C1-C12烷基；R代表例如由以下式子（II）表示的基团：其中，R2和R3独立地表示氢原子或C1-C8烷基；R4代表可取代的苯环、可取代的萘环、可取代的萘烷环、可取代的四氢萘环或选择自氧原子、硫原子和氮原子组成的1至4个杂环原子，并且总共有5至10个环构成原子的可选取代的杂环。
• 3-SUBSTITUTED-4-PYRIMIDONE DERIVATIVES
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1427709B1

  公开（公告）日：2005-12-14
• US7572793B2
  申请人：——

  公开号：US7572793B2

  公开（公告）日：2009-08-11
• [EN] 3-SUBSTITUTED-4-PYRIMIDONE DERIVATIVES<br/>[FR] DERIVES DE 3-SUBSTITUTE-4-PYRIMIDONE
  申请人：MITSUBISHI PHARMA CORP

  公开号：WO2003027080A1

  公开（公告）日：2003-04-03

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof having inhibitory activity against tau protein kinase 1:wherein R1 represents a C1-C12 alkyl group which may be substituted;R represents, for example, a group represented by the following formula (II):wherein R2 and R3 independently represent a hydrogen atom or a C1-C8 alkyl group; R4 represents a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.
• 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; A new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors
  作者：Kenji Fukunaga、Fumiaki Uehara、Keiichi Aritomo、Aya Shoda、Shinsuke Hiki、Masahiro Okuyama、Yoshihiro Usui、Kazutoshi Watanabe、Koichi Yamakoshi、Toshiyuki Kohara、Tokushi Hanano、Hiroshi Tanaka、Susumu Tsuchiya、Shinji Sunada、Ken-Ichi Saito、Jun-ichi Eguchi、Satoshi Yuki、Shoichi Asano、Shinji Tanaka、Akiko Mori、Keiji Yamagami、Hiroshi Baba、Takashi Horikawa、Masatake Fujimura

  DOI：10.1016/j.bmcl.2013.09.020

  日期：2013.12

  A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3β (GSK-3β). We found 21, 29 and 30 to possess potent in vitro GSK-3β inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.

  合成了一系列2-（2-苯基吗啉-4-基）嘧啶-4（3 H）-酮，并检查了它们对糖原合酶激酶-3β（GSK-3β）的抑制活性。我们发现21，29和30，以在体外具有GSK-3β在体外PK性能良好的抑制活性有效。21显示在小鼠口服后tau磷酸化显着降低，PK表现出色。