(5-甲氧基-1H-吲哚-2-基)-(3-甲氧基苯基)甲酮 | 370581-10-5

• 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
• 中文名称: (5-甲氧基-1H-吲哚-2-基)-(3-甲氧基苯基)甲酮
• 英文名称: D-68144
• 英文别名: (5-methoxy-1H-indol-2-yl)(3-methoxyphenyl)methanone；(5-methoxy-1H-indole-2-yl)-(3-methoxyphenyl)-methanone；5-methoxy-1H-2-indolyl(3-methoxyphenyl)-1-methanone；(5-methoxy-1H-indol-2-yl)-(3-methoxyphenyl)methanone
• CAS: 370581-10-5
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: SMIWRPKOZOIKAQ-UHFFFAOYSA-N

物化性质

• 熔点：
  147-148 °C
• 沸点：
  499.9±35.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(苯磺酰基)-5-甲氧基吲哚 在 重铬酸吡啶 、 正丁基锂 、 四丁基氟化铵 、 三氟乙酸吡啶 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (5-甲氧基-1H-吲哚-2-基)-(3-甲氧基苯基)甲酮
  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

• Substrate-Controlled Transformation of Azobenzenes to Indazoles and Indoles via Rh(III)-Catalysis
  作者：Shangjun Cai、Songyun Lin、Xiangli Yi、Chanjuan Xi

  DOI：10.1021/acs.joc.6b02548

  日期：2017.1.6

  excellent regio-selectivity are achieved in this reaction. Mechanistically, the reaction with acrylates undergoes β-hydride elimination, while the reaction with vinyl ketones or acrylamides undergoes nucleophilic addition. Copper acetate was supposed to play different roles in the β-hydride elimination to furnish indazoles and nucleophilic addition of C–Rh bond to deliver 2-acyl (NH) indoles.

  Rh（III）催化的底物控制的偶氮苯向吲唑和2-酰基（NH）吲哚的转化是通过CH官能团实现的。通常，在该反应中获得良好的官能团耐受性，令人满意的产率和优异的区域选择性。从机理上讲，与丙烯酸酯的反应经历β-氢化物消除，而与乙烯基酮或丙烯酰胺的反应经历亲核加成。醋酸铜据推测在消除β-氢化物以提供吲唑和亲核加成C-Rh键以生成2-酰基（NH）吲哚中起着不同的作用。
• Cyclic indole and heteroindole derivatives and methods for making and using as pharmaceuticals
  申请人：Weinberger Heinz

  公开号：US20050267303A1

  公开（公告）日：2005-12-01

  The invention relates to novel, substituted, fused indole and heteroindole derivatives of the general formula I their tautomers, stereoisomers, mixtures and pharmaceutically acceptable salts, their synthesis and their use as pharmaceuticals, especially as anti-tumor agents, for mammals, especially for man.

  本发明涉及新颖的、取代的、融合的吲哚和杂吲哚衍生物，其一般式I的互变异构体、立体异构体、混合物和药用盐，它们的合成以及它们作为药物的用途，特别是作为抗肿瘤剂，用于哺乳动物，尤其是用于人类。
• 2-acyl indole derivatives and their use as antitumor agents
  申请人：——

  公开号：US20020091124A1

  公开（公告）日：2002-07-11

  The invention relates to novel indole and heteroindole derivatives of the formula I 1 to their tautomers, their stereoisomers, their mixtures and their salts, to their preparation and to the use of indole derivatives of the formula I as antitumor agents.

  这项发明涉及到式I的新型吲哚和杂吲哚衍生物，以及它们的互变异构体、立体异构体、混合物和盐，以及它们的制备和将式I的吲哚衍生物用作抗肿瘤药剂。
• Synthetic 2-Aroylindole Derivatives as a New Class of Potent Tubulin-Inhibitory, Antimitotic Agents
  作者：Siavosh Mahboobi、Herwig Pongratz、Harald Hufsky、Jörg Hockemeyer、Markus Frieser、Alexei Lyssenko、Dietrich H. Paper、Jutta Bürgermeister、Frank-D. Böhmer、Heinz-Herbert Fiebig、Angelika M. Burger、Silke Baasner、Thomas Beckers

  DOI：10.1021/jm010940+

  日期：2001.12.1

  A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity Of IC50 = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, I did not significantly affect the GTPase activity of beta -tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.
• ANELLIERTE INDOL- UND HETEROINDOLDERIVATE, DEREN HERSTELLUNG UND VERWENDUNG ALS ANTITUMORMITTEL
  申请人：Zentaris GmbH

  公开号：EP1423393A1

  公开（公告）日：2004-06-02