2-Chlor-3-cyan-5-(pyrid-4-yl)pyridin | 70959-58-9

• 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: 2-Chlor-3-cyan-5-(pyrid-4-yl)pyridin
• 英文别名: 2-chloro-3-cyano-5-(4-pyridinyl)pyridine；6-Chloro-[3,4'-bipyridine]-5-carbonitrile；2-chloro-5-pyridin-4-ylpyridine-3-carbonitrile
• CAS: 70959-58-9
• 化学式: C₁₁H₆ClN₃
• 分子量: 215.642
• InChiKey: YYWUUBRRAZTHJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Chlor-3-cyan-5-(pyrid-4-yl)pyridin 在 过氧乙酸 、 溶剂黄146 作用下， 反应 4.0h， 以85%的产率得到6-chloro-5-cyano-(3,4'-bipyridine)-1'-oxide
  参考文献：
  名称：

  Synthesis and cardiotonic activity of 6-substituted 5-cyano-(3,4′-bipyridine)-1′-oxides and related compounds: molecular structure of 5-cyano-6-morpholino-(3,4′-bipyridine)-1′-oxide (AWD 122–239)

  摘要：

  6-Chloro-3,4'-bipyridine-1-oxides 5 and 5-cyano-1,6-dihydro-2-methyl-6-oxo-3,4'-bipyridine-1'-oxide 7 have been prepared from the corresponding pyridine derivatives by oxidation using peracetic acid. Reaction of 5 with various amines gave the 6-substituted compounds 6. Some of the synthesized products 6 were subsequently converted by derivation into related analogues 8, 9 and 10. In this series 5-cyano-6-morpholino-(3,4'-bipyridine)-1'-oxide (AWD 122-239, 6a), exhibited remarkable positive inotropic potency in spontaneously beating isolated guinea-pig atria as well as in anesthetized pigs. Additionally, 6a showed nearly no inhibition of cyclic AMP phosphodiesterase III. The molecular and crystal structures were determined together with the molecular electrostatic potential and structure-activity relationships are discussed. The obtained results clearly indicate compound 6a as a new type of cardiotonic.

  DOI：

  10.1016/0223-5234(94)90035-3
• 作为产物：
  描述：

  2-羟基-3-氰基吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 溴 、 sodium carbonate 、 溶剂黄146 、 三氯氧磷 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 13.0h， 生成 2-Chlor-3-cyan-5-(pyrid-4-yl)pyridin
  参考文献：
  名称：

  通过CAN508的支架跳跃发现新型CDK抑制剂

  摘要：

  细胞周期蛋白依赖性激酶（CDK）是各种人类疾病（尤其是癌症）的有希望的药物靶标。在已知的选择性CDK9抑制剂CAN508上应用了支架跳跃策略，合成了一系列吡唑并[3,4- b ]吡啶化合物，并在体外评估为CDK2和CDK9抑制剂。大多数化合物对CDK2 / cyclin A和CDK9 / cyclin T1系统均表现出中度至强效的抑制活性。其中，化合物2e的CD 50的IC 50值为0.36μM，而CDK9的IC 50值为1.8μM。值得注意的是，支架的改变似乎导致抑制剂的选择性变化。与CAN508相比，复合2k对CDK2表现出显着的选择性（是CDK9的265倍）。对化合物2k的对接研究为进一步设计更有效和选择性的CDK2 / CDK9抑制剂提供了提示。

  DOI：

  10.1016/j.bmcl.2018.02.054

文献信息

• Mild and Efficient Conversion of Nitriles to Amides with Basic Urea-Hydrogen Peroxide Adduct
  作者：Roman Balicki、Łukasz Kaczmarek

  DOI：10.1080/00397919308011173

  日期：1993.12

  Abstract The urea-hydrogen peroxide adduct, an inexpensive, stable and easily handled reagent has shown utility for mild and efficient transformation of nitriles into the corresponding aliphatic or aromatic amides. Reaction proceeds in aqueous acetone, within 0.5-2.5h, in the presence of catalytic amount of K2CO3, at room temperature.

  摘要 尿素-过氧化氢加合物是一种廉价、稳定且易于处理的试剂，可用于将腈温和有效地转化为相应的脂肪族或芳香族酰胺。反应在丙酮水溶液中进行，在 0.5-2.5 小时内，在催化量的 K2CO3 存在下，在室温下进行。
• 2-Substituted amino-5-(pyridinyl)-nicotinamides and their cardiotonic use
  申请人：Sterling Drug Inc.

  公开号：US04374141A1

  公开（公告）日：1983-02-15

  Shown is a process for preparing cardiotonically active 1,3-dihydro-3-R-6-PY-5-Q-2H-imidazo[4,5-b]pyridin-2-ones, where Q is hydrogen or lower-alkyl, R is lower-alkyl, lower-hydroxyalkyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene and NB is di-(lower-alkyl)amino or 4-morpholinyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, by reacting a 2-RNH-5-PY-6-Q-nicotinamide with an alkali metal hypohalite. Also shown are cardiotonic compositions and a method for increasing cardiac contractility using 2-RR'N-5-PY-6-Q-nicotinamides or pharmaceutically acceptable acid-addition salts thereof, where R' is hydrogen or methyl. Also shown is the process for preparing said 2-RR'N-5-PY-6-Q-nicotinamides by reacting a 2-halo-5-PY-6-Q-nicotinamide with an amine of the formula RR'NH.

  所示的是一种制备心力活性1,3-二氢-3-R-6-PY-5-Q-2H-咪唑[4,5-b]吡啶-2-酮的过程，其中Q是氢或低烷基，R是低烷基，低羟基烷基，低烷氧基烷基或Y-NB，其中Y是低烷基烯和NB是双-(低烷基)氨基或4-吗啉基，PY是4-或3-吡啶基或带有一个或两个取代基的4-或3-吡啶基，通过将2-RNH-5-PY-6-Q-烟酰胺与碱金属次氯酸盐反应来实现。还显示了心力活性组合物和一种利用2-RR'N-5-PY-6-Q-烟酰胺或其药用可接受的酸盐增加心脏收缩力的方法，其中R'是氢或甲基。还显示了通过将2-卤代-5-PY-6-Q-烟酰胺与RR'NH式胺反应制备所述2-RR'N-5-PY-6-Q-烟酰胺的过程。
• 5-(Pyridinyl)-1H-pyrazolo[3,4-b]pyridine-3-amines, their use as
  申请人：Sterling Drug Inc.

  公开号：US04264603A1

  公开（公告）日：1981-04-28

  1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with 1-R-hydrazine, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl or lower-alkoxyalkyl, 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 cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.

  用于作为心力增强剂的1-R-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶-3-胺或其药用可接受的酸盐，通过将2-卤代-5-PY-6-Q-烟酰腈与1-R-肼反应制备，其中R为氢、较低的烷基、较低的羟基烷基、2,3-二羟基丙基或较低的烷氧基烷基，Q为氢或较低的烷基，PY为4-或3-吡啶基或带有一个或两个较低的烷基取代基的4-或3-吡啶基。还显示了心力增强剂组合物和使用所述化合物或盐增加心脏收缩力的方法。
• 5-(Pyridinyl)-1H-pyrazolo[3,4-b]pyridin-3-amines and their cardiotonic
  申请人：Sterling Drug Inc.

  公开号：US04361568A1

  公开（公告）日：1982-11-30

  1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amine with a lower-alkanoic acid and reducing agent to produce 1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridine (I) where NB is NHR.sub.1 or NR.sub.1 R.sub.2, with a mixture of formic acid and formaldehyde to produce I where NB is N(CH.sub.3).sub.2 or with a lower-acylating agent to produce I where NB is NHAc and, if desired, reacting the 3-(NHAc) compound with a reducing agent to prepare the corresponding 3-NHR.sub.1 compound, where R is lower-alkyl, lower-hydroxyalkyl, lower-acyloxy-(lower-alkyl) or lower-alkoxy-alkyl, Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, and NB is selected from NHR.sub.1, NR.sub.1 R.sub.2 or NHAc where R.sub.1 and R.sub.2 are each lower-alkyl and Ac is lower-acyl. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.

  1-R-3-(NB)-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶或其药用酸盐，可作为心力衰竭药物，通过将1-R-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶-3-胺与低碳酸和还原剂反应制备出1-R-3-(NB)-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶(I)，其中NB为NHR.sub.1或NR.sub.1 R.sub.2，通过甲酸和甲醛的混合物产生I，其中NB为N(CH.sub.3).sub.2，或者通过低酰化剂产生I，其中NB为NHAc，并且如果需要，将3-(NHAc)化合物与还原剂反应以制备相应的3-NHR.sub.1化合物，其中R为低烷基、低羟基烷基、低酰氧基-(低烷基)或低烷氧基烷基，Q为氢或低烷基，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，NB选自NHR.sub.1、NR.sub.1 R.sub.2或NHAc，其中R.sub.1和R.sub.2各自为低烷基，Ac为低酰基。同时还展示了心力衰竭药物组合物和使用所述化合物或盐来增加心脏收缩力的方法。
• 2-(Substituted-amino)-5-(pyridinyl-nicotinonitriles, and their
  申请人：Sterling Drug Inc.

  公开号：US04362734A1

  公开（公告）日：1982-12-07

  Shown are cardiotonically active 2-RR'N-5-PY-6-Q-nicotinonitriles where R is methyl or ethyl, R' is hydrogen or methyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, and Q is hydrogen or methyl, the latter only when R' is hydrogen, or pharmaceutically acceptable acid-addition salts thereof. Also shown are cardiotonic compositions and a method for increasing cardiac contractility using as active components 2-RR'N-5-PY-6-Q-nicotinonitriles or pharmaceutically acceptable acid-addition salts thereof, where R, R', PY and Q are defined as above. Also shown is the process for preparing said 2-RR'N-5-PY-6-Q-nicotinonitriles by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with an amine of the formula RR'NH.

  展示的是具有心脏强心作用的2-RR'N-5-PY-6-Q-烟酰腙，其中R为甲基或乙基，R'为氢或甲基，PY为4-或3-吡啶基或带有一或两个取代基的4-或3-吡啶基，Q为氢或甲基，仅当R'为氢时才为甲基，或其药学上可接受的酸加成盐。还显示了心脏强心组合物和使用2-RR'N-5-PY-6-Q-烟酰腙或其药学上可接受的酸加成盐作为活性成分来增加心脏收缩力的方法，其中R、R'、PY和Q的定义如上所述。还显示了通过将2-卤代-5-PY-6-Q-烟酰腙与RR'NH的胺反应制备所述2-RR'N-5-PY-6-Q-烟酰腙的过程。