3-amino-1H-indazole-5-carbohydrazide | 1210843-88-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 3-amino-1H-indazole-5-carbohydrazide
• CAS: 1210843-88-1
• 化学式: C₈H₉N₅O
• 分子量: 191.192
• InChiKey: FAYMQLQCIJJSIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-1H-indazole-5-carbohydrazide 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-(3-amino-1H-indazol-5-yl)-N-benzyl-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  The optimization of aminooxadiazoles as orally active inhibitors of Cdc7

  摘要：

  A series of aminooxadiazoles was optimized for inhibition of Cdc7. Early lead isoquinoline 1 suffered from modest cell potency (cellular IC50 = 0.71 mu M measuring pMCM2), low selectivity against structurally related kinases, and high IV clearance in rats (CL = 18 L/h/kg). Extensive optimization resulted in azaindole 26 (Cdc7 IC50 = 1.1 nM, pMCM2 IC50 = 32 nM) that demonstrated robust lowering of pMCM2 in a mouse pharmacodynamic (PD) model when dosed orally. Modifications to improve the pharmacokinetic profile of this series were guided by trapping experiments with glutathione in rat hepatocytes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.055
• 作为产物：
  描述：

  3-氨基吲唑 在 aluminum (III) chloride 、 肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 3-amino-1H-indazole-5-carbohydrazide
  参考文献：
  名称：

  The optimization of aminooxadiazoles as orally active inhibitors of Cdc7

  摘要：

  A series of aminooxadiazoles was optimized for inhibition of Cdc7. Early lead isoquinoline 1 suffered from modest cell potency (cellular IC50 = 0.71 mu M measuring pMCM2), low selectivity against structurally related kinases, and high IV clearance in rats (CL = 18 L/h/kg). Extensive optimization resulted in azaindole 26 (Cdc7 IC50 = 1.1 nM, pMCM2 IC50 = 32 nM) that demonstrated robust lowering of pMCM2 in a mouse pharmacodynamic (PD) model when dosed orally. Modifications to improve the pharmacokinetic profile of this series were guided by trapping experiments with glutathione in rat hepatocytes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.055

文献信息

• [DE] INDAZOL-5-CARBONSÄUREHYDRAZID-DERIVATE<br/>[EN] INDAZOLE-5-CARBOXYLIC ACID HYDRAZIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'ACIDE INDAZOL-5-CARBOXYLIQUE
  申请人：MERCK PATENT GMBH

  公开号：WO2010020307A2

  公开（公告）日：2010-02-25

  Neue Indazolderivate der Formel (I) worin Ar, G, R, X1, X2, X3, Y und n die in Anspruch 1 angegebenen Bedeutungen haben, sind Kinase-Inhibitoren und können zur Behandlung von Krankheiten und Leiden wie Diabetes, Fettsucht, metabolisches Syndrom (Dyslipidämie), systemische und pulmonale Hypertonie, Herzkreislauferkrankungen und Nierenerkrankungen, allgemein bei jeglicher Art von Fibrosen, entzündlichen Prozessen, Tumoren und Tumorerkrankungen verwendet werden.
• The optimization of aminooxadiazoles as orally active inhibitors of Cdc7
  作者：Paul E. Harrington、Matthew P. Bourbeau、Christopher Fotsch、Michael Frohn、Alexander J. Pickrell、Andreas Reichelt、Kelvin Sham、Aaron C. Siegmund、Julie M. Bailis、Tammy Bush、Sonia Escobar、Dean Hickman、Scott Heller、Faye Hsieh、Jessica N. Orf、Minqing Rong、Tisha San Miguel、Helming Tan、Leeanne Zalameda、John G. Allen

  DOI：10.1016/j.bmcl.2013.09.055

  日期：2013.12

  A series of aminooxadiazoles was optimized for inhibition of Cdc7. Early lead isoquinoline 1 suffered from modest cell potency (cellular IC50 = 0.71 mu M measuring pMCM2), low selectivity against structurally related kinases, and high IV clearance in rats (CL = 18 L/h/kg). Extensive optimization resulted in azaindole 26 (Cdc7 IC50 = 1.1 nM, pMCM2 IC50 = 32 nM) that demonstrated robust lowering of pMCM2 in a mouse pharmacodynamic (PD) model when dosed orally. Modifications to improve the pharmacokinetic profile of this series were guided by trapping experiments with glutathione in rat hepatocytes. (C) 2013 Elsevier Ltd. All rights reserved.