5-(1-hydroxyethyl)-1,6-naphthyridin-2(1H)-one | 98617-13-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-(1-hydroxyethyl)-1,6-naphthyridin-2(1H)-one
• 英文别名: 5-(1-hydroxyethyl)-1H-1,6-naphthyridin-2-one
• CAS: 98617-13-1
• 化学式: C₁₀H₁₀N₂O₂
• 分子量: 190.202
• InChiKey: APXGYTXZRBBRTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(1-hydroxyethyl)-1,6-naphthyridin-2(1H)-one 在 二甲基亚砜 、 三氟乙酸酐 作用下， 以 氯仿 为溶剂， 以36%的产率得到5-acetyl-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Novel cAMP PDE III inhibitors: 1,6-naphthyridin-2(1H)-ones

  摘要：

  Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5). The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles. The C(5)-series was prepared from 5-acyl-6-[2-(dimethylamino)ethenyl]-2-(1H)-pyridinone (11), 5-bromo-1,6-naphthyridin-2(1H)-one (17), and 1,3-diketones 19 and 27. 1,6-Naphthyridin-2(1H)-ones are novel inhibitors of cAMP PDE III. Modification of the carbonyl group of 3 or N-methylation at N(1) resulted in a dramatic loss of enzyme activity. Absence of the C(5)-methyl group of medorinone (3) or its shift to C(3) or C(7) also resulted in reduced activity. Substitution at C(3) also diminished activity. However, substitution at C(5) by a wide variety of substituents led to improvement of enzyme activity and several C(5)-substituted analogs were more potent than milrinone.

  DOI：

  10.1021/jm00104a012
• 作为产物：
  描述：

  5-<1-(acetyloxy)ethyl>-1,6-naphthyridin-2(1H)-one 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以71%的产率得到5-(1-hydroxyethyl)-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Novel cAMP PDE III inhibitors: 1,6-naphthyridin-2(1H)-ones

  摘要：

  Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5). The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles. The C(5)-series was prepared from 5-acyl-6-[2-(dimethylamino)ethenyl]-2-(1H)-pyridinone (11), 5-bromo-1,6-naphthyridin-2(1H)-one (17), and 1,3-diketones 19 and 27. 1,6-Naphthyridin-2(1H)-ones are novel inhibitors of cAMP PDE III. Modification of the carbonyl group of 3 or N-methylation at N(1) resulted in a dramatic loss of enzyme activity. Absence of the C(5)-methyl group of medorinone (3) or its shift to C(3) or C(7) also resulted in reduced activity. Substitution at C(3) also diminished activity. However, substitution at C(5) by a wide variety of substituents led to improvement of enzyme activity and several C(5)-substituted analogs were more potent than milrinone.

  DOI：

  10.1021/jm00104a012

文献信息

• 1,6-Naphthyridin derivatives useful as cardiotonics and preparation thereof
  申请人：STERLING DRUG INC.

  公开号：EP0134535A1

  公开（公告）日：1985-03-20

  4-R'-5-Q-1,6-naphthyridin-2(1H)-ones (I), where R' is . hydrogen or methyl and Q is hydroxymethyl, 1-hydroxyethyl alkanoyloxymethyl or 1-alkanoyloxyethyl, are produced by first reacting 4-R'-5-acetyl (or n-propanoyl)-6-[2-(di- lower-alkylamino]-2(1H)-pyridinone (III) with hydroxylamine or salt thereof to produce 4-R'-5-Q'-1,6-naphthyridin-2(1H)-one-6-oxide (II), where R' is defined as above and Q' is methyl or ethyl; next reacting II with an alkanoic anhydride to produce I where Q is alkanoyloxymethyl or 1- alkanoyloxyethyl; and, then hydrolyzing said alkanoyloxymethyl or -ethyl compound to produce I where Q is hydroxymethyl or 1-hydroxyethyl. Also shown is the cardiotonic use of II and I where Q is hydroxymethyl, 1-hydroxyethyl or alkanoyloxymethyl.

  4-R'-5-Q-1,6-萘啶-2(1H)-酮 (I)，其中 R' 是 .氢或甲基，Q 为羟甲基、1-羟乙基烷酰氧基甲基或 1-烷酰氧基乙基、首先将 4-R'-5-乙酰基（或正丙酰基）-6-[2-（二低级烷基氨基）-2(1H)-吡啶酮（III）]与羟胺或其盐反应，生成 4-R'-5-Q'-1,6-萘啶-2(1H)-酮-6-氧化物（II），其中 R'定义如上，Q'为甲基或乙基；再将 II 与烷酸酐反应生成 I，其中 Q 为烷酰氧基甲基或 1-烷酰氧基乙基；然后，水解所述烷酰氧基甲基或-乙基化合物，生成 I，其中 Q 为羟甲基或 1-羟乙基。图中还显示了 II 和 I 的强心剂用途，其中 Q 为羟甲基、1-羟乙基或烷酰氧基甲基。
• LESHER, G. Y.;SINGH, BALDEV
  作者：LESHER, G. Y.、SINGH, BALDEV

  DOI：——

  日期：——
• US4532247A
  申请人：——

  公开号：US4532247A

  公开（公告）日：1985-07-30
• US4604399A
  申请人：——

  公开号：US4604399A

  公开（公告）日：1986-08-05
• Novel cAMP PDE III inhibitors: 1,6-naphthyridin-2(1H)-ones
  作者：Baldev Singh、George Y. Lesher、Kevin C. Pluncket、Edward D. Pagani、Donald C. Bode、Ross G. Bentley、Mary J. Connell、Linda T. Hamel、Paul J. Silver

  DOI：10.1021/jm00104a012

  日期：1992.12

  Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5). The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles. The C(5)-series was prepared from 5-acyl-6-[2-(dimethylamino)ethenyl]-2-(1H)-pyridinone (11), 5-bromo-1,6-naphthyridin-2(1H)-one (17), and 1,3-diketones 19 and 27. 1,6-Naphthyridin-2(1H)-ones are novel inhibitors of cAMP PDE III. Modification of the carbonyl group of 3 or N-methylation at N(1) resulted in a dramatic loss of enzyme activity. Absence of the C(5)-methyl group of medorinone (3) or its shift to C(3) or C(7) also resulted in reduced activity. Substitution at C(3) also diminished activity. However, substitution at C(5) by a wide variety of substituents led to improvement of enzyme activity and several C(5)-substituted analogs were more potent than milrinone.