1,2-dihydro-2-oxo-5-(4-pyridinyl)-1,6-naphthyridine-3-carboxylic acid | 102995-79-9

• 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: 1,2-dihydro-2-oxo-5-(4-pyridinyl)-1,6-naphthyridine-3-carboxylic acid
• 英文别名: 2-Oxo-5-(pyridin-4-yl)-1,2-dihydro-1,6-naphthyridine-3-carboxylic acid；2-oxo-5-pyridin-4-yl-1H-1,6-naphthyridine-3-carboxylic acid
• CAS: 102995-79-9
• 化学式: C₁₄H₉N₃O₃
• 分子量: 267.244
• InChiKey: GMNOYMIIMDJLRV-UHFFFAOYSA-N

物化性质

• 沸点：
  573.7±50.0 °C(Predicted)
• 密度：
  1.451±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-dihydro-2-oxo-5-(4-pyridinyl)-1,6-naphthyridine-3-carboxylic acid 反应 0.05h， 以72%的产率得到5-(4-pyridinyl)-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：

  1,2-dihydro-2-oxo-5-(4-pyridinyl)-1,6-naphthyridine-3-carbonitrile 在 sodium hydroxide 作用下， 反应 6.0h， 以88%的产率得到1,2-dihydro-2-oxo-5-(4-pyridinyl)-1,6-naphthyridine-3-carboxylic acid
  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-2(1H) - ones useful as cardiotonics and preparation thereof
  申请人：STERLING DRUG INC.

  公开号：EP0191298A2

  公开（公告）日：1986-08-20

  Naphthyridin-2(1 H)-ones, having the formula I or salts thereof, where Z is hydrogen or cyano, and Q is 2 (or 3)-furanyl, 2(or 3)-thienyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two methyl substituents, are useful as cardiotonic agents and corresponding compounds where Z is carboxy are useful as intermediates. Also shown as intermediates are 5-(Q-CO)-6-[2(di-lower-alkylamino)-ethenyl]-2(1H)-pyridinones (II) or salts thereof, where Q is defined as above. A process for preparing the compounds (I) comprises reacting a compound (II) with formamidine, ammonia or a salt thereof.

  萘啶-2(1H)-酮，具有式 I 或其盐，其中 Z 为氢或氰基，Q 为 2（或 3）-呋喃基、2（或 3）-噻吩基、4（或 3）-吡啶基或具有一个或两个甲基取代基的 4（或 3）-吡啶基，可用作强心剂，Z 为羧基的相应化合物可用作中间体。作为中间体的还有 5-(Q-CO)-6-[2(二低烷基氨基)-乙烯基]-2(1H)-吡啶酮 (II) 或其盐，其中 Q 的定义同上。制备化合物(I)的工艺包括使化合物(II)与甲脒，氨或其盐反应。
• LESHER, G. Y.;SINGH, B.
  作者：LESHER, G. Y.、SINGH, B.

  DOI：——

  日期：——
• US4567186A
  申请人：——

  公开号：US4567186A

  公开（公告）日：1986-01-28
• US4650806A
  申请人：——

  公开号：US4650806A

  公开（公告）日：1987-03-17
• 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.