3-氨基-1-甲基-5-吡啶-4-基吡啶-2-酮 | 62749-44-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-氨基-1-甲基-5-吡啶-4-基吡啶-2-酮
• 英文名称: 1-methyl-3-amino-5-(pyridin-4-yl)pyridin-2-one
• 英文别名: 5-amino-1-methyl-1H-[3,4']bipyridinyl-6-one；3-amino-1-methyl-5-(4-pyridinyl)-2(1H)-pyridinone；5-amino-1-methyl-[3,4'-bipyridin]-6(1H)-one；3-amino-1-methyl-5-pyridin-4-ylpyridin-2-one
• CAS: 62749-44-4
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: KXFHELHAHLKBTH-UHFFFAOYSA-N

物化性质

• 沸点：
  414.5±45.0 °C(Predicted)
• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-carbamido-1-methyl-5-(pyrid-4-yl)-1,2-dihydropyrid-2-one 在 sodium hypobromide 作用下， 以49%的产率得到3-氨基-1-甲基-5-吡啶-4-基吡啶-2-酮
  参考文献：
  名称：

  Hagen, V.; Klauschenz, E.; Pragst, F., Journal fur praktische Chemie (Leipzig 1954), 1987, vol. 329, # 5, p. 793 - 803

  摘要：

  DOI：
• 作为试剂：
  描述：

  1-methyl-5-nitro-1H-[3,4']bipyridinyl-6-one 、 2-羟基-3-硝基吡啶 在 钯 、 氢气 、 水 、 苯乙醇 、 3-氨基-1-甲基-5-吡啶-4-基吡啶-2-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 以leaving 10.1 g的产率得到3-氨基-1-甲基-5-吡啶-4-基吡啶-2-酮
  参考文献：
  名称：

  Preparation of 3-amino(or carbamyl)-5-(pyridinyl)-2(1H)-pyridinones

  摘要：

  可用作强心剂的化合物是1-R-3-Q-5-PY-2（1H）-吡啶酮（I），其中R是氢，低烷基或低羟基烷基，Q是氨基（优选），低烷基氨基，双（低烷基）氨基或NHAc，Ac是低烷酰基或低羧基烷基，PY是4-或3-或2-吡啶基或具有一或两个低烷基取代基的4-或3-或2-吡啶基。当Q为硝基，氨基甲酰基，氰基，卤素或氢时，相应的化合物可用作中间体，而当Q为氢或氰基时也可用作强心剂。这些化合物的制备方法包括：通过将.alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)丙烯醛（II）与马隆酰胺反应，制备1,2-二氢-2-氧代-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，制备3-氨基-5-PY-2（1H）-吡啶酮（Ib）；通过将II或.alpha.-PY-马隆醛（II'）与.alpha.-氰基乙酰胺反应，制备1,2-二氢-2-氧代-5-PY-烟酰腈（III），然后部分水解III制备Ia；通过将1,2-二氢-2-氧代-5-PY-烟酸（IV）与浓硫酸和浓硝酸混合物加热，制备3-硝基-5-PY-2（1H）-吡啶酮（Ic），然后将Ic还原为Ib，或先将Ic与烷基化试剂反应，制备1-R'-3-硝基-5-PY-2（1H）-吡啶酮（Id），然后将Id还原为1-R'-3-氨基-5-PY-2（1H）-吡啶酮（Ib），其中R'为低烷基或低羟基烷基。还展示了Q为氨基的其他衍生物。

  公开号：

  US04225715A1

文献信息

• 5-(Pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04107315A1

  公开（公告）日：1978-08-15

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮（I），其中R是氢、低烷基或低羟基烷基，Q是氨基（首选）、低烷基氨基、二（低烷基）氨基或NHAc，Ac是低脂肪酰基或低羰基脂肪酸酯，PY是具有一个或两个低烷基取代基的4-或3-或2-吡啶基或4-或3-或2-吡啶基。Q为硝基、氨基甲酰基、氰基、卤素或氢的相应化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物的制备方法包括：通过将.alpha.-PY-.beta.-(R1R2N)丙烯醛（II）与马来酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮（Ib）；通过将II或.alpha.-PY-马隆醛（II'）与.alpha.-氰基乙酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰腈（III），然后部分水解III，生成Ia；通过将1,2-二氢-2-氧-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，生成3-硝基-5-PY-2(1H)-吡啶酮（Ic），然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮（Id），再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮（Ib），其中R'是低烷基或低羟基烷基。显示了Q为氨基的I的其他衍生物。
• 3-Amino-5-(pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04072746A1

  公开（公告）日：1978-02-07

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  作为强心药剂有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮（I），其中R是氢、低烷基或低羟基烷基，Q是氨基（首选）、低烷基氨基、二（低烷基）氨基或NHAc，Ac是低烷酰基或低羰基烷氧基，PY是4-或3-或2-吡啶基或带有一个或两个低烷基取代基的4-或3-或2-吡啶基。相应的化合物中，如果Q是硝基、氨基甲酰基、氰基、卤素或氢，则可用作中间体；其中Q是氢或氰基的化合物也可用作强心药剂。所述化合物的制备方法包括：通过将α-PY-β-(R1R2N)丙烯醛（II）与马来酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮（Ib）；通过将II或α-PY-马隆醛（II'）与α-氰基乙酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酸腈（III），然后部分水解III，生成Ia；通过将1,2-二氢-2-氧-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，生成3-硝基-5-PY-2(1H)-吡啶酮（Ic），然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应，生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮（Id），然后将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮（Ib），其中R'是低烷基或低羟基烷基。展示了Q是氨基的I的其他衍生物。
• Di-(lower-alkyl)
  申请人：Sterling Drug Inc.

  公开号：US04199586A1

  公开（公告）日：1980-04-22

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehye (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotininc acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Ic to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  有用作心脏强心剂的化合物是1-R-3-Q-5-PY-2（1H）-吡啶酮（I），其中R为氢，低烷基或低羟基烷基，Q为氨基（优选），低烷基氨基，二（低烷基）氨基或NHAc，Ac为低烷酰基或低羧烷氧基，PY为4-或3-或2-吡啶基或4-或3-或2-吡啶基，具有一个或两个低烷基取代基。当Q为硝基，氨基甲酰基，氰基，卤素或氢时，相应的化合物可用作中间体，当Q为氢或氰基时，也可用作心脏强心剂。所述化合物的制备方法是：通过将α-PY-β-（R1R2N）丙烯醛（II）与马隆酰胺反应，产生1,2-二氢-2-氧代-5-PY-烟酰胺（Ia），并用能将氨基甲酰基转化为氨基的试剂反应Ia，以产生3-氨基-5-PY-2（1H）-吡啶酮（Ib）；通过将II或α-PY-马隆醛（II'）与α-氰乙酰胺反应，产生1,2-二氢-2-氧代-5-PY-烟酰腈（III），并部分水解III以产生Ia；通过将1,2-二氢-2-氧代-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，产生3-硝基-5-PY-2（1H）-吡啶酮（Ic），然后将Ic还原以产生Ib，或首先将Ic与烷基化试剂反应以产生1-R'-3-硝基-5-PY-2（1H）-吡啶酮（Id），然后将Ic还原以产生1-R'-3-氨基-5-PY-2（1H）-吡啶酮（Ib），其中R'为低烷基或低羟基烷基。还展示了Q为氨基的I的其他衍生物。
• Synthesis and profiling of a 3-aminopyridin-2-one-based kinase targeted fragment library: Identification of 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one scaffold for monopolar spindle 1 (MPS1) and Aurora kinases inhibition
  作者：Daren Fearon、Isaac M. Westwood、Rob L.M. van Montfort、Richard Bayliss、Keith Jones、Vassilios Bavetsias

  DOI：10.1016/j.bmc.2018.04.033

  日期：2018.7

  Screening a 3-aminopyridin-2-one based fragment library against a 26-kinase panel representative of the human kinome identified 3-amino 5 (1-methyl-1H-pyrazol-4-yl)pyridin-2(1H)-one (2) and 3-amino-5(pyridin-4-yl)pyridin-2(1H)-one (3) as ligand efficient inhibitors of the mitotic kinase Monopolar Spindle 1 (MPS1) and the Aurora kinase family. These kinases are well recognised as attractive targets for therapeutic intervention for treating cancer. Elucidation of the binding mode of these fragments and their analogues has been carried out by X-ray crystallography. Structural studies have identified key interactions with a conserved lysine residue and have highlighted potential regions of MPS1 which could be targeted to improve activity and selectivity. (C) 2018 The Authors. Published by Elsevier Ltd.
• Multi-API Loading Prodrugs
  申请人：Zeidan Tarek A.

  公开号：US20120202823A1

  公开（公告）日：2012-08-09

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.