1-(4-pyridinyl)-2-(dimethylamino)ethenyl methyl ketone | 78504-61-7

• 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
• 英文名称: 1-(4-pyridinyl)-2-(dimethylamino)ethenyl methyl ketone
• 英文别名: (Z)-4-(dimethylamino)-3-pyridin-4-ylbut-3-en-2-one
• CAS: 78504-61-7
• 化学式: C₁₁H₁₄N₂O
• 分子量: 190.245
• InChiKey: QEJJLSDONYSIPV-DHZHZOJOSA-N

物化性质

• 熔点：
  118.5-122.0 °C
• 沸点：
  340.5±42.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1-(4-pyridinyl)-2-(dimethylamino)ethenyl methyl ketone 在 硫酸 、 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 生成 米力农杂质A
  参考文献：
  名称：

  Bipyridine cardiotonics: the three-dimensional structures of amrinone and milrinone

  摘要：

  The cardiotonic drug milrinone (1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile) is superior to its analogue amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) by virtue of its greater potency and reduced side effect profile. We confirmed initial reports on the potencies of milrinone and amrinone and found that after intravenous administration to phenobarbital anesthetized dogs, the drugs had cumulative inotropic ED50's of 37 and 1891 micrograms/kg, respectively; relative effects on heart rate and blood pressure were comparable. There are two structural differences between amrinone and milrinone: (1) milrinone has a pyridone 2-methyl substituent and (2) the pyridone 5-amino substituent of amrinone is replaced with a nitrile in milrinone. We confirmed structure-activity studies that indicated that the 2-methyl substituent appears to be primarily responsible for the dramatic difference in the potencies of amrinone and milrinone. A plausible explanation for the effect of the methyl substituent is an altered molecular topology resulting from its steric interaction with the 3',5'-hydrogen atoms. Consequently, we probed the three-dimensional structures of these two compounds by X-ray crystallography. The dihedral angle between the planes formed by the two aromatic rings of amrinone was 1.3 degrees. In marked contrast, the corresponding angle for milrinone was 52.2 degrees. Moreover, 1H NMR studies revealed conformational differences in solution. Whereas the 2-methyl substituent undoubtedly produces some electronic and hydrophobic perturbations in the bipyridine cardiotonic series, the most significant effect, from a global viewpoint, is the altered molecular topology.

  DOI：

  10.1021/jm00155a009
• 作为产物：
  描述：

  4-甲基吡啶 在 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 1-(4-pyridinyl)-2-(dimethylamino)ethenyl methyl ketone
  参考文献：
  名称：

  Bipyridine cardiotonics: the three-dimensional structures of amrinone and milrinone

  摘要：

  The cardiotonic drug milrinone (1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile) is superior to its analogue amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) by virtue of its greater potency and reduced side effect profile. We confirmed initial reports on the potencies of milrinone and amrinone and found that after intravenous administration to phenobarbital anesthetized dogs, the drugs had cumulative inotropic ED50's of 37 and 1891 micrograms/kg, respectively; relative effects on heart rate and blood pressure were comparable. There are two structural differences between amrinone and milrinone: (1) milrinone has a pyridone 2-methyl substituent and (2) the pyridone 5-amino substituent of amrinone is replaced with a nitrile in milrinone. We confirmed structure-activity studies that indicated that the 2-methyl substituent appears to be primarily responsible for the dramatic difference in the potencies of amrinone and milrinone. A plausible explanation for the effect of the methyl substituent is an altered molecular topology resulting from its steric interaction with the 3',5'-hydrogen atoms. Consequently, we probed the three-dimensional structures of these two compounds by X-ray crystallography. The dihedral angle between the planes formed by the two aromatic rings of amrinone was 1.3 degrees. In marked contrast, the corresponding angle for milrinone was 52.2 degrees. Moreover, 1H NMR studies revealed conformational differences in solution. Whereas the 2-methyl substituent undoubtedly produces some electronic and hydrophobic perturbations in the bipyridine cardiotonic series, the most significant effect, from a global viewpoint, is the altered molecular topology.

  DOI：

  10.1021/jm00155a009

文献信息

• Lower-alkyl 2-halo-5-(pyridinyl)nicotinates, their preparation and use
  申请人：Sterling Drug Inc.

  公开号：US04264612A1

  公开（公告）日：1981-04-28

  Cardiotonic composition and method for increasing cardiac contractility using an effective amount of a cardiotonic lower-alkyl 2-halo-5-PY-6-Q'-nicotinate or pharmaceutically-acceptable acid-addition salt thereof, where halo is chloro or bromo, Q' is hydrogen or lower-alkyl and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are novel lower-alkyl 2-halo-5-PY-6-(lower-alkyl)nicotinates or pharmaceutically-acceptable acid-addition salt thereof, useful as intermediates or cardiotonics and preparation thereof.

  心力衰竭组合物及增加心脏收缩力的方法，使用有效量的心力衰竭低烷基2-卤代-5-PY-6-Q'-烟酸盐或其药用可接受的酸盐，其中卤代是氯或溴，Q'是氢或低烷基，PY是4-或3-吡啶基或4-或3-吡啶基，具有一个或两个低烷基取代基。还显示了新型的低烷基2-卤代-5-PY-6-(低烷基)烟酸盐或其药用可接受的酸盐，可用作中间体或心力衰竭药物和其制备方法。
• 1,2-Dihydro-5-pyridinyl-3H-pyrazolo[3,4-b]pyridin-3-ones and their use
  申请人：Sterling Drug Inc.

  公开号：US04265895A1

  公开（公告）日：1981-05-05

  1,2-Dihydro-1-R-5-PY-6-Q-3H-pyrazolo[3,4-b]pyridin-3-ones or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonic agents, are prepared by reacting lower-alkyl 2-halo-5-PY-6-Q-nicotinate with 1-R-hydrazine. Also disclosed are cardiotonic compositions and method for increasing cardiotonic contractility using said compounds or salts.

  1,2-二氢-1-R-5-PY-6-Q-3H-吡唑并[3,4-b]吡啶-3-酮或其药用可接受的酸盐，可用作心力增强剂，通过将低烷基2-卤代-5-PY-6-Q-烟酸酯与1-R-肼反应制备。还公开了心力增强剂组合物和使用所述化合物或盐增加心力增强性的方法。
• 5-(Pyridinyl)-6-(lower-alkyl)-2(1H)-pyridinones,
  申请人：Sterling Drug Inc.

  公开号：US04312875A1

  公开（公告）日：1982-01-26

  1-R.sub.1 -6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones or 1-R.sub.1 -1,2-dihydro-2-oxo-6-(lower-alkyl)-5-(pyridinyl)nicotinic acids or lower-alkyl esters thereof or pharmaceutically-acceptable acid-addition or cationic salts thereof are useful as cardiotonic agents, where R.sub.1 is hydrogen, lower-alkyl or lower-hydroxyalkyl. These compounds are prepared by hydrolyzing the corresponding 3-cyano compounds to produce the corresponding 3-carboxylic acids and then either by decarboxylating or esterifying the acids.

  1-R.sub.1 -6-(较低烷基)-5-(吡啶基)-2(1H)-吡啶酮或1-R.sub.1 -1,2-二氢-2-氧代-6-(较低烷基)-5-(吡啶基)烟酸或其较低烷基酯或其药用可接受的酸加合物或阳离子盐作为强心剂。其中R.sub.1是氢、较低烷基或较低羟基烷基。这些化合物通过水解相应的3-氰基化合物制备相应的3-羧基酸，然后通过脱羧或酯化酸来制备。
• Compositions and their preparation
  申请人：Sterling Drug Inc.

  公开号：US04276293A1

  公开（公告）日：1981-06-30

  2-R.sub.2 -3-R.sub.3 -6-PY-5-Q-3H-imidazo[4,5-b]pyridines (I) or 1-R.sub.1 -2-R.sub.2 -6-PY-5-Q-1H-imidazo[4,5-b]pyridines (IA) or pharmaceutically-acceptable acid-addition salts thereof, where Q and R.sub.2 are each hydrogen or lower-alkyl, R.sub.1 and R.sub.3 are each hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene having at least two carbon atoms between its connecting linkages and NB is di-(lower-alkyl)amino or 4-morpholinyl, at least one of R.sub.1 or R.sub.3 being hydrogen, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, which are useful as cardiotonics, are prepared by reacting 2-R.sub.3 NH-3-R.sub.1 NH-5-PY-6-Q-pyridine (II) with a tri-(lower-alkyl) ortho-(lower-alkanoate). Also shown are: the use of I or IA or salts in cardiotonic compositions and a method for increasing cardiac contractility; and, the preparation of the intermediates II, as well as intermediates used to prepare II.

  2-R.sub.2 -3-R.sub.3 -6-PY-5-Q-3H-咪唑并[4,5-b]吡啶（I）或1-R.sub.1 -2-R.sub.2 -6-PY-5-Q-1H-咪唑并[4,5-b]吡啶（IA）或其药用可接受的酸盐，其中Q和R.sub.2分别为氢或低烷基，R.sub.1和R.sub.3分别为氢、低烷基、低羟基烷基、2,3-二羟基丙基、低烷氧基烷基或Y-NB，其中Y为至少在其连接链之间具有两个碳原子的低烷基，NB为二（低烷基）氨基或4-吗啉基，R.sub.1或R.sub.3中至少一个为氢，PY为4-或3-吡啶基或带有一个或两个低烷基取代基的4-或3-吡啶基，这些化合物可用作心力衰竭药物，通过将2-R.sub.3 NH-3-R.sub.1 NH-5-PY-6-Q-吡啶（II）与三（低烷基）邻-(低烷酸酯)反应制备。还显示了：在心力衰竭药物组合物中使用I或IA或盐以及增加心脏收缩力的方法；以及用于制备II的中间体II的制备，以及用于制备II的中间体。
• 5-(Pyridinyl)pyridine-2,3-diamines, preparation thereof and their
  申请人：Sterling Drug Inc.

  公开号：US04297360A1

  公开（公告）日：1981-10-27

  2-R.sub.3 RN-3-R.sub.1 R'N-5-PY-6-Q-pyridines (I) or pharmaceutically-acceptable acid-addition salts thereof are useful as intermediates in the preparation of 1- or 3-substituted-1,3-dihydro-5-Q-6-PY-2H-imidazo[4,5-b]pyridin-2-ones or -2-thiones and also as intermediates for preparing 1- or 3-substituted-5-Q-6-PY-3H(or 1H)-imidazo[4,5-b]pyridines, where R.sub.1, R.sub.3, R, R', PY and Q are defined hereinbelow. Also shown are processes for preparing I and the following intermediates used therein: 2-halo-3-nitro-5-PY-6-Q-pyridines (III), 2-R.sub.3 RN-3-nitro-5-PY-6-Q-pyridines (V), 2-halo-5-PY-6-Q-pyridines (VII), 2-R.sub.3 RN-5-PY-6-Q-pyridines (VIII) and 2-R.sub.3 RN-3-halo-5-PY-6-Q-pyridines (IX) or salts thereof. Certain embodiments of II and VIII also are useful as cardiotonics and are shown as active components of cardiac compositions and methods for increasing cardiac contractility.

  2-R.sub.3 RN-3-R.sub.1 R'N-5-PY-6-Q-吡啶类化合物（I）或其药用可接受的酸盐在制备1-或3-取代-1,3-二氢-5-Q-6-PY-2H-咪唑[4,5-b]吡啶-2-酮或-2-硫酮以及制备1-或3-取代-5-Q-6-PY-3H（或1H）-咪唑[4,5-b]吡啶的中间体中是有用的，其中R.sub.1、R.sub.3、R、R'、PY和Q的定义如下。还显示了制备I及其中使用的以下中间体的过程：2-卤代-3-硝基-5-PY-6-Q-吡啶类化合物（III）、2-R.sub.3 RN-3-硝基-5-PY-6-Q-吡啶类化合物（V）、2-卤代-5-PY-6-Q-吡啶类化合物（VII）、2-R.sub.3 RN-5-PY-6-Q-吡啶类化合物（VIII）和2-R.sub.3 RN-3-卤代-5-PY-6-Q-吡啶类化合物（IX）或其盐。II和VIII的某些实施例也可用作强心剂，并显示为心脏组合物的活性成分和增加心脏收缩力的方法。