5-(3-amino-1H-indazol-5-yl)-N-benzyl-1,3,4-oxadiazol-2-amine | 1041480-95-8

• 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: 5-(3-amino-1H-indazol-5-yl)-N-benzyl-1,3,4-oxadiazol-2-amine
• CAS: 1041480-95-8
• 化学式: C₁₆H₁₄N₆O
• 分子量: 306.327
• InChiKey: AUIUHHYHJAGFBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氨基吲唑 在 aluminum (III) chloride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 肼 作用下， 以 甲醇 、 二氯甲烷 、 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

文献信息

• 5-(1,3,4-OXADIAZOL-2-YL)-1H-INDAZOLE AND 5-(1,3,4-THIADIAZOL-2-YL)-1H-INDAZOLE DERIVATIVES AS SGK INHIBITORS FOR THE TREATMENT OF DIABETES
  申请人：Klein Markus

  公开号：US20100063115A1

  公开（公告）日：2010-03-11

  Novel aminoindazolylurea derivatives of the formula (I), in which L, X, Y, R 3 , R 4 and R 5 have the meanings indicated in Claim 1, are SGK inhibitors and can be used for the treatment of SGK-induced diseases and complaints, such as diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in fibroses and inflammatory processes of any type.

  新型氨基吲唑基脲衍生物的化学式（I），其中L、X、Y、R3、R4和R5具有权利要求1中指示的含义，是SGK抑制剂，可用于治疗由SGK引起的疾病和不适，如糖尿病、肥胖、代谢综合征（血脂异常）、全身和肺动脉高压、心血管疾病和肾脏疾病，通常用于任何类型的纤维化和炎症过程。
• 5-([1,3,4]OXADIAZOL-2-YL)-1H-INDAZOL UND 5-([1,3,4]THIADIAZOL-2-YL)-1H-INDAZOL DERIVATE ALS SGK-INHIBITOREN ZUR BEHANDLUNG VON DIABETES
  申请人：Merck Patent GmbH

  公开号：EP2102197B1

  公开（公告）日：2011-07-13
• [DE] 5-([1,3,4] 0XADIAZ0L-2-YL)-1H-INDAZOL UND 5-([1,3,4] THIADIAZ0L-2-YL)-1H-INDAZOL DERIVATE ALS SGK-INHIBITOREN ZUR BEHANDLUNG VON DIABETES<br/>[EN] 5-([1,3,4] OXADIAZOL-2-YL)-1H-INDAZOL AND 5-([1,3,4] THIADIAZOL-2-YL)-1H-INDAZOL DERIVATIVES AS SGK INHIBITORS FOR THE TREATMENT OF DIABETES<br/>[FR] DÉRIVÉS DE 5-( [1, 3, 4] OXADIAZOLE-2-YL)-IH-INDAZOLE ET 5-( [1, 3, 4] THIADIAZOLE-2-YL)-IH-INDAZOLE COMME INHIBITEURS DE LA SGK POUR LE TRAITEMENT DE DIABÈTES
  申请人：MERCK PATENT GMBH

  公开号：WO2008086854A1

  公开（公告）日：2008-07-24

  [EN] Disclosed are novel aminoindazole urea derivatives of formula (I), wherein L, X, Y, R³, R⁴ and R⁵ have the meanings indicated in claim 1. Said aminoindazole urea derivatives are SGK inhibitors and can be used for the treatment of SGK-induced diseases and ailments such as diabetes, obesity, metabolic syndrome (dyslipidemia), systemic and pulmonary hypertension, cardiovascular diseases, and kidney diseases, more generally for any kind of fibroses and inflammatory processes.
  [FR] L'invention concerne de nouveaux dérivés d'urée d'aminoindazole de formule (I), où L, X, Y, R³, R⁴ et R⁵ ont les significations indiquées dans la revendication 1. Ces nouveaux dérivés sont des inhibiteurs de la SGK et peuvent être utilisés pour le traitement de maladies et affections liées à la SGK comme le diabète, l'obésité, le syndrome métabolique (dyslipidémie), l'hypertonie généralisée et pulmonaire, les maladies cardio-vasculaires et les maladies rénales, et d'une manière générale pour tous types de fibroses et de processus inflammatoires.
  [DE] Neue Aminoindazolharnstoffderivate der Formel (I) worin L, X, Y, R³, R⁴ und R⁵ die in Anspruch 1 angegebenen Bedeutungen haben, sind SGK-Inhibitoren und können zur Behandlung von SGK-bedingten Krankheiten und Leiden wie Diabetes, Fettsucht, metabolisches Syndrom (Dyslipidämie), systemische und pulmonale Hypertonie, Herzkreislauferkrankungen und Nierenerkrankungen, allgemein bei jeglicher Art von Fibrosen und entzündlichen Prozessen 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.