5-[(2R)-2-hydroxy-2-phenylethanoyl]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate | 827318-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-[(2R)-2-hydroxy-2-phenylethanoyl]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate
• 英文别名: ethyl 5-[(2R)-2-hydroxy-2-phenylacetyl]-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-1-carboxylate
• CAS: 827318-96-7
• 化学式: C₂₈H₃₂N₆O₅
• 分子量: 532.599
• InChiKey: XPYOBSBAIBJDFH-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-[(2R)-2-hydroxy-2-phenylethanoyl]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate 在 甲醇 、 三乙胺 作用下， 反应 3.0h， 生成 PHA-E429
  参考文献：
  名称：

  1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles:  Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile

  摘要：

  The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.

  DOI：

  10.1021/jm060897w
• 作为产物：
  描述：

  3-氨基-5-叔丁氧羰基-吡咯并[3,4-C]吡唑 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 5-[(2R)-2-hydroxy-2-phenylethanoyl]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate
  参考文献：
  名称：

  1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles:  Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile

  摘要：

  The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.

  DOI：

  10.1021/jm060897w

文献信息

• Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
  申请人：Fancelli Daniele

  公开号：US20060276471A1

  公开（公告）日：2006-12-07

  Pyrrolo[3,4-c]pyrazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  本发明公开了式(I)的吡咯并[3,4-c]吡唑衍生物及其药学上可接受的盐的制备方法和包含它们的制药组合物；本发明中的化合物可能在治疗与蛋白激酶活性失调有关的疾病，如癌症中有用。
• PYRROLO 3,4-c PYRAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS
  申请人：NERVIANO MEDICAL SCIENCES S.R.L.

  公开号：EP1644376B1

  公开（公告）日：2010-09-08
• US7141568B2
  申请人：——

  公开号：US7141568B2

  公开（公告）日：2006-11-28
• US7582628B2
  申请人：——

  公开号：US7582628B2

  公开（公告）日：2009-09-01
• [EN] PYRROLO[3,4-c]PYRAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS<br/>[FR] DERIVES DU PYRROLO[3,4-C]PYRAZOLE ACTIFS COMME INHIBITEURS DES KINASES
  申请人：PHARMACIA ITALIA SPA

  公开号：WO2005005427A1

  公开（公告）日：2005-01-20

  [EN] Pyrrolo[3,4-c]pyrazole derivatives of formula (1) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
  [FR] L'invention porte: sur des dérivés du pyrrolo[3,4-c]pyrazole de formule (I) et leurs sels pharmacocompatibles, tels que définis dans la spécification; sur leur procédé de préparation; et sur des préparations pharmaceutiques les comprenant. Lesdits composés peuvent servir en thérapie au traitement de maladies, associées à un dérèglement de l'activité des protéines kinases, telles que le cancer.