2-tert-butyl-1'-(1H-indazole-5-carbonyl)-4,6-dihydrospiro-[indazole-5,4'-piperidin]-7(2H)-one | 1307297-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-tert-butyl-1'-(1H-indazole-5-carbonyl)-4,6-dihydrospiro-[indazole-5,4'-piperidin]-7(2H)-one
• 英文别名: 2-tert-butyl-1'-(1H-indazole-5-carbonyl)-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one；2-tert-butyl-1'-(1H-indazole-5-carbonyl)spiro[4,6-dihydroindazole-5,4'-piperidine]-7-one
• CAS: 1307297-39-7
• 化学式: C₂₃H₂₇N₅O₂
• 分子量: 405.5
• InChiKey: VBVYLVOZUYQCLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  benzyl 2-tert-butyl-2,4-dihydrospiro[indazole-5,4'-piperidine]-1'-carboxylate 在 palladium 10% on activated carbon N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 、 甲酸铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.75h， 生成 2-tert-butyl-1'-(1H-indazole-5-carbonyl)-4,6-dihydrospiro-[indazole-5,4'-piperidin]-7(2H)-one
  参考文献：
  名称：

  [EN] N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
  [FR] INHIBITEURS DE N2-PYRAZOLOSPIROCÉTONE ACÉTYL-COA CARBOXYLASE

  摘要：

  该发明提供了化合物(I)的结构或该化合物的药用盐，其中R1、R2、R3和R4如本文所述；以及其药物组合物；以及在治疗受乙酰辅酶A羧化酶抑制调节的动物疾病、症状或紊乱中的应用。

  公开号：

  WO2011058473A1

文献信息

• N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
  申请人：Bagley Scott William

  公开号：US20120225900A1

  公开（公告）日：2012-09-06

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of said compound, wherein R 1 , R 2 , R 3 and R 4 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

  本发明提供了式(I)的化合物或其药学上可接受的盐，其中R1、R2、R3和R4如本文所述；其药物组合物；以及在治疗动物中通过抑制乙酰辅酶A羧化酶酶的作用调节的疾病、症状或疾患中使用该化合物的方法。
• Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors
  作者：Scott W. Bagley、James A. Southers、Shawn Cabral、Colin R. Rose、David J. Bernhardson、David J. Edmonds、Jana Polivkova、Xiaojing Yang、Daniel W. Kung、David A. Griffith、Scott J. Bader

  DOI：10.1021/jo202377g

  日期：2012.2.3

  Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.