D-65500 | 370581-20-7

• 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: D-65500
• 英文别名: (4-chlorophenyl)-(5-methoxy-1H-indole-2-yl)-methanone；5-methoxy-1H-2-indolyl(4-chlorophenyl)-1-methanone；(4-Chloro-phenyl)-(5-methoxy-1H-indol-2-yl)-methanone；(4-chlorophenyl)-(5-methoxy-1H-indol-2-yl)methanone
• CAS: 370581-20-7
• 化学式: C₁₆H₁₂ClNO₂
• 分子量: 285.73
• InChiKey: NJTGNWPBTVIKNI-UHFFFAOYSA-N

物化性质

• 沸点：
  487.9±35.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  D-65500 在 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 1.0h， 生成 1-(4-chlorophenyl)-6-methoxy-2-phenyl-3a-aza-cyclopenta[a]indene-3-one
  参考文献：
  名称：

  Cyclic indole and heteroindole derivatives and methods for making and using as pharmaceuticals

  摘要：

  这项发明涉及一种新颖的、取代的、融合的吲哚和杂吲哚衍生物，其一般式为I1，它们的互变异构体、立体异构体、混合物和药学上可接受的盐，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，特别是人类。

  公开号：

  US20040039197A1
• 作为产物：
  描述：

  1-(苯磺酰基)-5-甲氧基吲哚 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.5h， 生成 D-65500
  参考文献：
  名称：

  Synthetic 2-Aroylindole Derivatives as a New Class of Potent Tubulin-Inhibitory, Antimitotic Agents

  摘要：

  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.

  DOI：

  10.1021/jm010940+

文献信息

• 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。
• 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
• [DE] CYCLISCHE INDOL-UND HETEROINDOLDERVIATE, DEREN HERSTELLUNG UND VERWENDUNG ALS ARZNEIMITTEL<br/>[EN] CYCLIC INDOLE AND HETEROINDOLE DERIVATIVES, THE PRODUCTION AND USE THEREOF AS MEDICAMENTS<br/>[FR] DERIVES CYCLIQUES D'INDOLE ET D'HETEROINDOLE, LEUR PRODUCTION ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：ZENTARIS AG

  公开号：WO2003020731A1

  公开（公告）日：2003-03-13

  Die Erfindung betrifft neue substituierte, anellierte Indol- und Heteroindolderivate der allgemeinen Formel (I) deren Tautomere, deren Stereoisomere, deren Gemische und deren pharmazeutisch annehmbaren Salze, deren Herstellung und deren Verwendung als Arzneimittel insbesondere als Antitumormittel, bei Säugetieren, insbesondere beim Menschen.
• 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.
• 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。