tert-butyl 1-isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazole-5,4'-piperidine]-1'-carboxylate | 1268521-74-9

• 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: tert-butyl 1-isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazole-5,4'-piperidine]-1'-carboxylate
• 英文别名: tert-butyl 7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4'-piperidine]-1'-carboxylate
• CAS: 1268521-74-9
• 化学式: C₁₉H₂₉N₃O₃
• 分子量: 347.458
• InChiKey: JRQQDCDIUOWSDI-UHFFFAOYSA-N

物化性质

• 沸点：
  483.9±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazole-5,4'-piperidine]-1'-carboxylate 在 甲醇 、 三乙胺 、 乙酰氯 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 生成 1,4-二氢-1'-[2-甲基-1H-苯并咪唑-6-基)羰基]-1-(1-甲基乙基)-螺[5H-吲唑-5,4'-哌啶]-7(6H)-一
  参考文献：
  名称：

  N1-Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors

  摘要：

  该发明提供了化合物I的化合物或其药用可接受的盐，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、症状或紊乱中的使用。

  公开号：

  US20110111046A1
• 作为产物：
  描述：

  tert-butyl 10-((dimethylamino)methylene)-9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 8.33h， 生成 tert-butyl 1-isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazole-5,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jo202377g

文献信息

• [EN] N1-PYRAZOLOSPIROKETONE ACETYL-CoA CARBOXYLASE INHIBITORS<br/>[FR] INHIBITEURS DE N1-PYRAZOLOSPIROCÉTONE ACÉTYL-COA CARBOXYLASE
  申请人：PFIZER

  公开号：WO2012042433A1

  公开（公告）日：2012-04-05

  The invention provides a compound of Formula (I) Z N N O N O A1R2 R1 R3R 3 L A 2 (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3,Z, A1, L and A 5 2 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.

  该发明提供了化合物Formula (I) Z N N O N O A1R2 R1 R3R 3 L A 2 (I)或该化合物的药用可接受的盐，其中R1、R2、R3、Z、A1、L和A 5 2如本文所述；其药物组成物；以及在治疗受乙酰辅酶A羧化酶抑制调节的动物疾病、状况或障碍中的使用。
• [EN] USE OF ACETYL-COA CARBOXYLASE INHIBITORS FOR TREATING ACNE VULGARIS<br/>[FR] UTILISATION D'INHIBITEURS DE L'ACÉTYL-COA CARBOXYLASE POUR TRAITER L'ACNÉ VULGAIRE
  申请人：PFIZER

  公开号：WO2015036892A1

  公开（公告）日：2015-03-19

  The present invention relates to methods of treating and/or preventing acne in patients comprising the step of administering to patients in need of such treatment a therapeutically effective amount of an ACC inhibitor or a pharmaceutically acceptable salt thereof.

  本发明涉及治疗和/或预防痤疮的方法，包括向需要此类治疗的患者施用治疗有效量的ACC抑制剂或其药用盐。
• N1-PYRAZOLOSPIROKETONE ACETYL-CoA CARBOXYLASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20130296319A1

  公开（公告）日：2013-11-07

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the 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.

  本发明提供一种式（I）的化合物或化合物的药学上可接受的盐，其中R1、R2、R3和R4如本文所述；以及其制成的药物组合物，并用于治疗动物体内受到乙酰辅酶A羧化酶酶抑制调节的疾病、病状或疾病。
• USE OF ACETYL-COA CARBOXYLASE INHIBITORS FOR TREATING ACNE VULGARIS
  申请人：PFIZER INC.

  公开号：US20160220557A1

  公开（公告）日：2016-08-04

  The present invention relates to methods of treating and/or preventing acne in patients comprising the step of administering to patients in need of such treatment a therapeutically effective amount of an ACC inhibitor or a pharmaceutically acceptable salt thereof.

  本发明涉及一种治疗和/或预防痤疮的方法，包括向需要此类治疗的患者施用治疗有效量的ACC抑制剂或其药学上可接受的盐。
• N1-pyrazolospiroketone acetyl-CoA carboxylase inhibitors
  申请人：PFIZER INC.

  公开号：US10294225B2

  公开（公告）日：2019-05-21

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3, Z, A1, L and A2 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.

  本发明提供了一种式 (I) 的化合物 或该化合物的药学上可接受的盐，其中 R1、R2、R3、Z、A1、L 和 A2 如本文所述；其药物组合物；及其在治疗受动物体内乙酰-CoA 羧化酶抑制调节的疾病、病症或失调中的用途。