1-amino-3-(2-pyridinyl)isoquinoline | 37989-04-1

• 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-amino-3-(2-pyridinyl)isoquinoline
• 英文别名: 3-(pyridin-2-yl)isoquinolin-1-amine；3-pyridin-2-yl-isoquinolin-1-ylamine；Isoquinoline, 1-amino-3-(2-pyridyl)-；3-pyridin-2-ylisoquinolin-1-amine
• CAS: 37989-04-1
• 化学式: C₁₄H₁₁N₃
• 分子量: 221.261
• InChiKey: SZYOCGSGLNKIQO-UHFFFAOYSA-N

物化性质

• 熔点：
  152-153 °C(Solv: methanol (67-56-1))
• 沸点：
  439.3±45.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-amino-3-(2-pyridinyl)isoquinoline 在 硫酸 、 氨 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 N-(3-Pyridin-2-yl-isoquinolin-1-yl)-formamidine
  参考文献：
  名称：

  A Novel Class of Adenosine A₃ Receptor Ligands. 1. 3-(2-Pyridinyl)isoquinoline Derivatives

  摘要：

  A series of 3-(2-pyridinyl)isoquinoline derivatives was synthesized as potential antagonists for the human adenosine A(3) receptor by substitution of the 1-position. The compounds were obtained by various synthetic routes from 1-amino-3-(2-pyridinyl)isoquinoline. The affinity was determined in radioligand binding assays for rat brain A(1) and A(2A) receptors and for the cloned human A(3) receptor. A structure-activity relationship analysis indicated that a phenyl group when coupled by a spacer allowing conjugation on position 1 of the isoquinoline ring increased the adenosine A(3) receptor affinity. In contrast, such a phenyl group directly bound to position 1 of the isoquinoline ring decreased affinity. Since the combination of a phenyl group together with a spacer raised adenosine A(3) receptor affinity, various spacers were investigated. VUF8501 (N-[3-(2-pyridinyl)isoquinolin-1-yl]benzamidine (15) showed an affinity at the human adenosine A(3) receptor of 740 nM. Substituent effects on the phenyl group were investigated by in vitro evaluation of a series of substituted benzamidines. Electron-donating groups at the para position of the benzamidine ring increased adenosine A(3) receptor affinity. These investigations led to VUF8505 (4-methoxy-N-[3-(2-pyridinyl)isoquinolin-1-yl]benzamidine (22)), which is a moderately potent and selective ligand for the human adenosine A(3) receptor with an affinity of 310 nM in our test system having negligible affinity for rat A(1) and A(2A) receptors.

  DOI：

  10.1021/jm980036q
• 作为产物：
  描述：

  2-氰基吡啶 、 邻甲基苯腈 在 氨 、 potassium amide 、 ferric nitrate 作用下， 以 四氢呋喃 为溶剂， 以58%的产率得到1-amino-3-(2-pyridinyl)isoquinoline
  参考文献：
  名称：

  一类新型的腺苷A3受体配体。2.一系列异喹啉和喹唑啉化合物的结构亲和力曲线。

  摘要：

  1-取代的3-（2-吡啶基）异喹啉已显示形成一类新型的腺苷A3受体配体。在本研究中，对这种新的前导物和此类化合物的结构亲和关系进行了进一步的研究。首先，确定异喹啉环的1位上的酰胺基对腺苷A3受体亲和力的影响。羧酰胺被证明是在异喹啉和苯环之间的有用的间隔基。N- [2-（2-吡啶基）异喹啉-4-基]苯甲酰胺（VUF8507，化合物6）对腺苷A3受体的亲和力为200 nM。其次，我们研究了用一系列单和双取代的N- [3-（2-吡啶基）异喹啉]苯甲酰胺取代6的苯甲酰胺环的影响。通过光谱技术（IR和NMR）测定固态和溶液中苯甲酰胺的互变异构体的比例。在大鼠脑A1和A2A受体以及克隆的人A3受体的放射性配体结合测定中确定亲和力。苯甲酰胺显示出比​​脂族酰胺更高的腺苷A3受体亲和力。我们建议，不同的苯甲酰胺的腺苷A3受体亲和力与其在亚氨基或酰胺形式中的存在有关。亚氨基形式的配体显示出较高的腺苷A3受体

  DOI：

  10.1021/jm980037i

文献信息

• Isoquinoline and Quinazoline Urea Analogues as Antagonists for the Human Adenosine A₃ Receptor
  作者：Jacqueline E. van Muijlwijk-Koezen、Henk Timmerman、Henk van der Goot、Wiro M. P. B. Menge、Jacobien Frijtag von Drabbe Künzel、Miriam de Groote、Adriaan P. IJzerman

  DOI：10.1021/jm000002u

  日期：2000.6.1

  substituted phenylurea analogues was investigated. Substituents such as electron-withdrawing or electron-donating groups were introduced at different positions of the benzene ring to probe electronic and positional effects of substitution. Substitution on the 3- or 4-position of the phenyl ring decreased the adenosine A(3) receptor affinity. Substitution at position 2 with an electron-donating substituent

  发现异喹啉和喹唑啉脲衍生物与人腺苷A（3）受体结合。合成了一系列N-苯基-N'-喹唑啉-4-基脲衍生物和N-苯基-N'-异喹啉-1-基脲衍生物，并在放射性配体结合试验中对其腺苷受体亲和力进行了测试。结构亲和力分析表明，与未取代或脂族衍生物相比，在喹唑啉环的2位或异喹啉环的等效3位上，苯基或杂芳基取代基增加了腺苷A（3）受体的亲和力。此外，研究了取代的苯基脲类似物的结构亲和性关系。在苯环的不同位置引入了诸如吸电子基团或供电子基团之类的取代基，以探测取代的电子和位置效应。苯环的3或4位上的取代降低了腺苷A（3）受体的亲和力。在第2位上被供电子取代基（例如甲基或甲氧基）取代，人腺苷A（3）受体亲和力增加，而在2位上用吸电子取代基取代不影响亲和力。这两个系列中的最佳取代基的组合具有累加作用，从而导致有效的人腺苷A（3）受体拮抗剂N-（2-甲氧基苯基）-N'-（2-（3-吡啶基）喹唑啉-4- yl）
• Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2-pyridyl)isoquinoline derivatives. 2. Amidines
  作者：Marcel A. H. De Zwart、Henk Van der Goot、Henk Timmerman

  DOI：10.1021/jm00122a033

  日期：1989.2

  2-3 times more active than the corresponding amides. Furthermore it was established that for these compounds too, the presence of a 2,2'-bipyridyl moiety is a necessary prerequisite for antimycoplasmal activity. As for the amides, antimycoplasmal activity of amidines derived from 1 is dependent on the hydrophobic fragmental value of the aromatic nucleus of the amidine moiety. A quantitative structure-activity

  在我们寻找具有抗支原体活性的新化合物的过程中，合成了一系列衍生自1-氨基-3-（2-吡啶基）异喹啉（1）的芳族s。在40 microM铜的存在下，最具活性的化合物在纳摩尔范围内显示出对鸡毒支原体的生长抑制。这些化合物的活性是泰乐菌素的3倍，泰乐菌素是兽医实践中使用的抗支原体治疗剂。在铜的存在下，衍生自1的am的活性是相应酰胺的2-3倍。此外，已经确定对于这些化合物而言，存在2,2'-联吡啶基部分是抗支原体活性的必要先决条件。至于酰胺，衍生自1的am的抗支原体活性取决于the部分的芳香核的疏水片段值。
• Aminoisoquinolines
  申请人：——

  公开号：US03991063A1

  公开（公告）日：1976-11-09

  New amino-isoquinoline derivatives of the general formula: ##SPC1## Wherein R.sub.1 and R.sub.4 are the same or different and each represents a hydrogen or halogen atom or an alkyl group, R.sub.2 and R.sub.3 are the same or different and each represents a hydrogen or halogen atom or an alkyl or alkoxy group or R.sub.2 and R.sub.3 together represent a methylenedioxy radical, R.sub.5 represents a hydrogen atom or an alkyl or aryl group and R.sub.6 represents a di (lower alkyl) amino group or a nitrogen containing 5- or 6-membered heterocyclic radical linked to the isoquinoline nucleus either through a carbon atom or through the nitrogen atom such as 2-, 3- or 4-pyridyl, or 1-pyrrolidinyl are described. The aforesaid alkyl and alkoxy groups are preferably lower alkyl and lower alkoxy groups respectively. By the terms "lower alkyl" and "lower alkoxy" as used in this specification are meant straight or branched chain alkyl and alkoxy groups respectively having at most 6 carbon atoms. The preferred aryl group, which may be represented by R.sub.5, is phenyl. The compounds appear effective in respiratory or oxidative processes in living organisms. When R.sub. 6 contains certain nitrogen moieties such as dialkylamino, and certain nitrogen heterocycles are effective economic poisons i.e. rodenticides, bacteriocides and fungicides. In less than toxic doses, the compounds are useful in combatting Chronic Respiratory Disease in poultry and in combatting barbiturate-induced respiratory failure.

  新的氨基异喹啉衍生物的一般式为：##SPC1## 其中，R.sub.1和R.sub.4相同或不同，每个代表氢或卤素原子或烷基，R.sub.2和R.sub.3相同或不同，每个代表氢或卤素原子或烷基或烷氧基，或R.sub.2和R.sub.3共同代表亚甲二氧基基团，R.sub.5代表氢原子或烷基或芳基，R.sub.6代表二（低烷基）氨基团或通过碳原子或氮原子与异喹啉核连接的含氮5-或6-成员杂环基团，例如2-、3-或4-吡啶基或1-吡咯基。上述烷基和烷氧基基团优选为低烷基和低烷氧基基团，分别具有最多6个碳原子的直链或支链烷基和烷氧基基团。优选的芳基，可以由R.sub.5代表，是苯基。这些化合物在生物体内的呼吸或氧化过程中似乎有效。当R.sub.6含有某些氮基团，例如二烷基氨基，和某些氮杂环时，它们是有效的经济毒药，即杀鼠剂、杀菌剂和杀真菌剂。在不致毒性的剂量下，这些化合物对于治疗家禽的慢性呼吸道疾病和治疗巴比妥类引起的呼吸衰竭非常有用。
• Alkaline-Metal-Promoted Divergent Synthesis of 1-Aminoisoquinolines and Isoquinolines
  作者：Peng Ma、Yuhang Wang、Ning Ma、Jianhui Wang

  DOI：10.1021/acs.joc.3c02384

  日期：2024.1.19

  Alkaline-metal-promoted divergent syntheses of 1-aminoisoquinolines and isoquinolines have been reported involving 2-methylaryl aldehydes, nitriles, and LiN(SiMe3)2 as reactants. In addition, the three-component reaction of 2-methylaryl nitriles, aldehydes, and LiN(SiMe3)2 has been developed to furnish 1-aminoisoquinolines. This protocol features readily available starting materials, excellent chemoselectivity

  碱金属促进的1-氨基异喹啉和异喹啉的不同合成已被报道，涉及2-甲基芳基醛、腈和LiN(SiMe 3 ) 2作为反应物。此外，还开发了2-甲基芳基腈、醛和LiN(SiMe 3 ) 2的三组分反应以提供1-氨基异喹啉。该方案具有易于获得的起始材料、优异的化学选择性、广泛的底物范围和令人满意的产率。
• Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2-pyridyl)isoquinoline derivatives. 1. Amides
  作者：Marcel A. H. De Zwart、Henk Van der Goot、Henk Timmerman

  DOI：10.1021/jm00399a005

  日期：1988.4

  In order to investigate the antimycoplasmal activity of compounds structurally related to 2,2'-bipyridyl, a series of both aliphatic and aromatic amides derived from 1-amino-3-(2-pyridyl)isoquinoline were synthesized. The most active compounds appeared to be as active as Tylosin, an antimycoplasmal therapeutic that is used in veterinary practice, in the presence of a small nontoxic amount of copper. Furthermore, it was found that antimycoplasmal activity depends on the hydrophobic fragmental value of amide residue. A quantitative structure-activity relationship established the optimal hydrophobic fragmental value of the amide residue to be 0.30.