2,4-dimethoxyphenyl-(1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-methanone | 370580-92-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4-dimethoxyphenyl-(1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-methanone
• 英文别名: 1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl(2,4-dimethoxyphenyl)-1-methanone；[1-(Benzenesulfonyl)pyrrolo[2,3-b]pyridin-2-yl]-(2,4-dimethoxyphenyl)methanone
• CAS: 370580-92-0
• 化学式: C₂₂H₁₈N₂O₅S
• 分子量: 422.461
• InChiKey: BMZOWSPHJAJHOU-UHFFFAOYSA-N

物化性质

• 熔点：
  180-190 °C (decomp)
• 沸点：
  675.7±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  95.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-dimethoxyphenyl-(1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-methanone 在 aq. 10percent NaOH 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 (1H-pyrrolo[2,3-b]pyridin-2-yl)-(2,4-dimethoxyphenyl)-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：

  7-氮杂吲哚-1-苯磺酰胺 、 2,4-二甲氧基苯甲酰氯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 2,4-dimethoxyphenyl-(1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-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+

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
• VERWENDUNG VON 2−ACYLINDOLEN ZUR BEHANDLUNG VON TUMOREN
  申请人：Baxter Healthcare SA

  公开号：EP1442015A1

  公开（公告）日：2004-08-04
• [DE] VERWENDUNG VON 2-ACYLINDOLEN ZUR BEHANDLUNG VON TUMOREN<br/>[EN] USE OF 2-ACYLINDOLES IN THE TREATMENT OF TUMORS<br/>[FR] UTILISATION DE 2-ACYLINDOLES POUR TRAITER DES TUMEURS
  申请人：BAXTER HEALTHCARE SA

  公开号：WO2003037861A1

  公开（公告）日：2003-05-08

  Die Erfindung betrifft die Verwendung der Indol- und Heteroindolderivate der allgemeinen Formel (I), deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, zur Herstellung eines Arzneimittels zur Behandlung von therapie-resistenten Tumoren, metastasierenden Tumoren und/oder als Angiogenesehemmer.