1-(Methylthio)-3-pyridin-2-ylisoquinoline

• 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-(Methylthio)-3-pyridin-2-ylisoquinoline
• 英文别名: 1-methylsulfanyl-3-pyridin-2-ylisoquinoline
• 化学式: C₁₅H₁₂N₂S
• 分子量: 252.34
• InChiKey: DMEAEJHGTAEIKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(Methylthio)-3-pyridin-2-ylisoquinoline 在 potassium permanganate 、 溶剂黄146 作用下， 以42%的产率得到1-Methanesulfonyl-3-pyridin-2-yl-isoquinoline
  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：

  甲硫醇 、 1-Chloro-3-(2-pyridyl)isoquinoline 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 14.0h， 以94%的产率得到1-(Methylthio)-3-pyridin-2-ylisoquinoline
  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

文献信息

• A Novel Class of Adenosine A₃ Receptor Ligands. 1. 3-(2-Pyridinyl)isoquinoline Derivatives
  作者：Jacqueline E. van Muijlwijk-Koezen、Henk Timmerman、Regina Link、Henk van der Goot、Adriaan P. IJzerman

  DOI：10.1021/jm980036q

  日期：1998.10.1

  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.

表征谱图