4-isochinolinyl-(5-methoxy-1-phenylsulfonyl-1H-2-indolyl)-methanol | 370580-21-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-isochinolinyl-(5-methoxy-1-phenylsulfonyl-1H-2-indolyl)-methanol
• 英文别名: 4-isoquinolinyl(5-methoxy-1-phenylsulfonyl-1H-2-indolyl)-1-methanol；[1-(Benzenesulfonyl)-5-methoxyindol-2-yl]-isoquinolin-4-ylmethanol
• CAS: 370580-21-5
• 化学式: C₂₅H₂₀N₂O₄S
• 分子量: 444.511
• InChiKey: AUCAYAXDRSOMIM-UHFFFAOYSA-N

物化性质

• 熔点：
  138-139 °C
• 沸点：
  723.8±70.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  89.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-isochinolinyl-(5-methoxy-1-phenylsulfonyl-1H-2-indolyl)-methanol 在 重铬酸吡啶 、 三氟乙酸吡啶 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 4-isoquinolinyl-(5-methoxy-1H-2-indolyl)-methanone
  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+
• 作为产物：
  描述：

  异喹啉-4-甲醛 、 1-(苯磺酰基)-5-甲氧基吲哚 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以64%的产率得到4-isochinolinyl-(5-methoxy-1-phenylsulfonyl-1H-2-indolyl)-methanol
  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。
• 2-ACYL-INDOLDERIVATE UND DEREN VERWENDUNG ALS ANTITUMORMITTEL
  申请人：Baxter Healthcare S.A.

  公开号：EP1276720B1

  公开（公告）日：2006-12-20
• 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.