5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-6-oxo-1H-imidazo[4,5-f]indole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-6-oxo-1H-imidazo[4,5-f]indole
• 英文别名: 5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-5,7-dihydro-3H-imidazo[4,5-f]indol-6-one；5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-1H,5H,6H,7H-imidazo[4,5-f]indol-6-one；5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-f]benzimidazol-6-one
• 化学式: C₁₇H₁₉N₅O
• 分子量: 309.371
• InChiKey: QRFIOQPCVMNZPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  77.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5,6-diamino-1-ethyl-3,3-dimethylindol-2-one 、 5-甲基-1H-吡唑-3-羧酸 在 PPA 、 四磷十氧化物 作用下， 反应 6.0h， 以20%的产率得到5-ethyl-7,7-dimethyl-2-(5-methyl-1H-pyrazol-3-yl)-6-oxo-1H-imidazo[4,5-f]indole
  参考文献：
  名称：

  A Pentacyclic Aurora Kinase Inhibitor (AKI-001) with High in Vivo Potency and Oral Bioavailability

  摘要：

  Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B enzymes, excellent cellular potency (IC50 < 100 nM), and good oral bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B are inhibited at inhibitor concentrations sufficient to block proliferation. Importantly, the cellular activity translates to potent inhibition of tumor growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near stasis (92% TGI) in an HCT116 mouse xenograft model.

  DOI：

  10.1021/jm800052b

文献信息

• Tricycles, their manufacture and use as pharmaceutical agents
  申请人：Guy Georges

  公开号：US20060069145A1

  公开（公告）日：2006-03-30

  The present invention relates to compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.

  本发明涉及公式I化合物及其药用可接受的盐、对映体形式、非对映异构体和混合物，上述化合物的制备，含有它们的药物以及其制造，以及上述化合物在控制或预防癌症等疾病中的用途。
• 三環式化合物、それら製造方法、及び医薬剤としての使用
  申请人：エフ.ホフマン−ラ ロシュ アーゲー

  公开号：JP2008514565A

  公开（公告）日：2008-05-08

  本発明の目的は、式（I）によって表される化合物、及びそれらの互変異性体、医薬として許容される塩、エナンチオマー型、ジアステレオマーと、ラセミ体、上述の化合物の調製、それらを含む医薬品とそれらの製造方法、並びに病気、例えば癌の管理又は予防における、又は対応する医薬品の製造における上述の化合物の使用である。

  本发明的目的是提供制备式（I）代表的化合物及其同系物、药学上可接受的盐、对映体、非对映体和外消旋体、上述化合物、含有它们的医药产品及其制造方法，以及它们在治疗或预防疾病（例如癌症）或在相应的上述化合物在制造医药产品中的用途。
• TRICYCLES, THEIR MANUFACTURE AND USE AS PHARMACEUTICAL AGENTS
  申请人：F. Hoffmann-Roche AG

  公开号：EP1793822A1

  公开（公告）日：2007-06-13
• US7285569B2
  申请人：——

  公开号：US7285569B2

  公开（公告）日：2007-10-23
• [EN] TRICYCLES, THEIR MANUFACTURE AND USE AS PHARMACEUTICAL AGENTS<br/>[FR] TRICYCLES, FABRICATION DE CEUX-CI ET UTILISATION DE CEUX-CI COMME AGENTS PHARMACEUTIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2006032519A1

  公开（公告）日：2006-03-30

  Objects of the present invention are the compounds of Formula (I) their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.