methyl 1-[4-(4-methylpiperazin-1-ylbenzoyl)]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-1H-thieno[3,2-c]pyrazole-5-carboxylate | 648411-41-0

• 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: methyl 1-[4-(4-methylpiperazin-1-ylbenzoyl)]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-1H-thieno[3,2-c]pyrazole-5-carboxylate
• 英文别名: Methyl 1-[4-(4-methylpiperazin-1-yl)benzoyl]-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]thieno[3,2-c]pyrazole-5-carboxylate
• CAS: 648411-41-0
• 化学式: C₃₁H₃₅N₇O₄S
• 分子量: 601.729
• InChiKey: LNNFSZBMSKFEFK-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 1-[4-(4-methylpiperazin-1-ylbenzoyl)]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-1H-thieno[3,2-c]pyrazole-5-carboxylate 在 甲醇 、 三乙胺 作用下， 反应 6.0h， 以4.6 g的产率得到3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

  摘要：

  A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

  DOI：

  10.1016/j.bmc.2010.07.048
• 作为产物：
  描述：

  4-(4-methylpiperazin-1-yl)benzoyl chloride dihydrochloride 、 3-氨基-1H-噻吩[3,2-C]吡唑-5-羧酸甲酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 1-[4-(4-methylpiperazin-1-ylbenzoyl)]-3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-1H-thieno[3,2-c]pyrazole-5-carboxylate
  参考文献：
  名称：

  Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

  摘要：

  A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

  DOI：

  10.1016/j.bmc.2010.07.048

文献信息

• [EN] HETEROBICYCLIC PYRAZOLE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES DE PYRAZOLE HETEROBICYCLIQUES UTILISES COMME INHIBITEURS DE KINASE
  申请人：PHARMACIA ITALIA SPA

  公开号：WO2004007504A1

  公开（公告）日：2004-01-22

  Bicyclo-pyrazoles of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, 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.

  公开了规范中定义的化学式(I)的双环吡唑及其药用盐，其制备方法和包含它们的药物组合物；发明中的化合物可能在治疗中对治疗与蛋白激酶活性失调相关的疾病，如癌症，具有用处。
• HETEROBICYCLIC PYRAZOLE DERIVATIVES AS KINASE INHIBITORS
  申请人：Pharmacia Italia S.p.A.

  公开号：EP1534716A1

  公开（公告）日：2005-06-01
• US7485661B2
  申请人：——

  公开号：US7485661B2

  公开（公告）日：2009-02-03