N-2-naphthyl-5-methoxy-1H-2-indolecarboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-2-naphthyl-5-methoxy-1H-2-indolecarboxamide
• 英文别名: 5-methoxy-N-naphthalen-2-yl-1H-indole-2-carboxamide
• 化学式: C₂₀H₁₆N₂O₂
• 分子量: 316.359
• InChiKey: LRCQBWOXBYBJIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-甲氧基吲哚-2-羧酸 、 2-萘胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以86%的产率得到N-2-naphthyl-5-methoxy-1H-2-indolecarboxamide
  参考文献：
  名称：

  Bis(1H-2-indolyl)methanones as a Novel Class of Inhibitors of the Platelet-Derived Growth Factor Receptor Kinase

  摘要：

  The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone group as well as substitution at both indoles result in weak or no activity. An ATP binding site model, derived by homology from the FGFR-1 tyrosine kinase crystal structure suggesting hydrogen bonds of one indole NH and the methanone oxygen with the backbone carbonyl and amide, respectively, of Cys684, explains why only one indole moiety is open for substitution and locates groups in the 5- or 6-position outside the pocket. The hitherto most active derivatives, 39, 53 and 67, inhibit both isoforms of the PDGF receptor kinase in intact cells, with IC50 of 0.1-0.3 muM, and purified PDGFbeta-receptor in vitro, with IC50 of 0.09, 0.1, or 0.02 muM, respectively. PDGF-stimulated DNA synthesis is inhibited by these derivatives with IC50 values of 1-3 muM. Kinetic analysis of 53 showed an ATP-competitive mode of inhibition. The compounds are inactive or weakly active toward a number of other tyrosine kinases, including the FGF receptor 1, EGF receptor, and c-Src kinase, as well as toward serine-threonine kinases, including different PKC isoforms and GRK2, and appear therefore selective for PDGF receptor inhibition.

  DOI：

  10.1021/jm010988n

文献信息

• Bis(1<i>H</i>-2-indolyl)methanones as a Novel Class of Inhibitors of the Platelet-Derived Growth Factor Receptor Kinase
  作者：Siavosh Mahboobi、Steffen Teller、Herwig Pongratz、Harald Hufsky、Andreas Sellmer、Alexander Botzki、Andrea Uecker、Thomas Beckers、Silke Baasner、Christoph Schächtele、Florian Überall、Matthias U. Kassack、Stefan Dove、Frank-D. Böhmer

  DOI：10.1021/jm010988n

  日期：2002.2.1

  The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone group as well as substitution at both indoles result in weak or no activity. An ATP binding site model, derived by homology from the FGFR-1 tyrosine kinase crystal structure suggesting hydrogen bonds of one indole NH and the methanone oxygen with the backbone carbonyl and amide, respectively, of Cys684, explains why only one indole moiety is open for substitution and locates groups in the 5- or 6-position outside the pocket. The hitherto most active derivatives, 39, 53 and 67, inhibit both isoforms of the PDGF receptor kinase in intact cells, with IC50 of 0.1-0.3 muM, and purified PDGFbeta-receptor in vitro, with IC50 of 0.09, 0.1, or 0.02 muM, respectively. PDGF-stimulated DNA synthesis is inhibited by these derivatives with IC50 values of 1-3 muM. Kinetic analysis of 53 showed an ATP-competitive mode of inhibition. The compounds are inactive or weakly active toward a number of other tyrosine kinases, including the FGF receptor 1, EGF receptor, and c-Src kinase, as well as toward serine-threonine kinases, including different PKC isoforms and GRK2, and appear therefore selective for PDGF receptor inhibition.