tert-butyl 2'-methyl-7'-oxo-6',7'-dihydro-1H,2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazole]-1-carboxylate | 1355229-02-5

• 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 2'-methyl-7'-oxo-6',7'-dihydro-1H,2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazole]-1-carboxylate
• 英文别名: tert-butyl 2-methyl-7-oxospiro[6H-pyrano[3,2-c]pyrazole-5,4'-piperidine]-1'-carboxylate
• CAS: 1355229-02-5
• 化学式: C₁₆H₂₃N₃O₄
• 分子量: 321.376
• InChiKey: OCYVWUHLKUVGFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2'-methyl-7'-oxo-6',7'-dihydro-1H,2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazole]-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以75%的产率得到2'-methyl-2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one hydrochloride
  参考文献：
  名称：

  Maximizing Lipophilic Efficiency: The Use of Free-Wilson Analysis in the Design of Inhibitors of Acetyl-CoA Carboxylase

  摘要：

  This paper describes the design and synthesis of a novel series of dual inhibitors of acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2). Key findings include the discovery of an initial lead that was modestly potent and subsequent medicinal chemistry optimization with a focus on lipophilic efficiency (LipE) to balance overall druglike properties. Free-Wilson methodology provided a clear breakdown of the contributions of specific structural elements to the overall LipE, a rationale for prioritization of virtual compounds for synthesis, and a highly successful prediction of the LipE of the resulting analogues. Further preclinical assays, including in vivo malonyl-CoA reduction in both rat liver (ACC1) and rat muscle (ACC2), identified an advanced analogue that progressed to regulatory toxicity studies.

  DOI：

  10.1021/jm201503u
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 1-(4-hydroxy-1-methyl-1H-pyrazol-3-yl)ethan-1-one 在 四氢吡咯 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以50%的产率得到tert-butyl 2'-methyl-7'-oxo-6',7'-dihydro-1H,2'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazole]-1-carboxylate
  参考文献：
  名称：

  [EN] PYRAZOLOSPIROKETONE ACETYL-C0A CARBOXYLASE INHIBITORS
  [FR] INHIBITEURS DE LA PYRAZOLOSPIROCÉTONE ACÉTL-COA CARBOXYLASE

  摘要：

  本发明提供了式(1)的化合物或所述化合物的药用可接受盐，其中R1、R2和R3如本文所述；其药物组合物；以及用于治疗通过抑制动物中的乙酰辅酶A羧化酶酶活性来调节的疾病、病症或障碍的使用方法。

  公开号：

  WO2009144554A1

文献信息

• [EN] PYRAZOLOSPIROKETONE ACETYL-C0A CARBOXYLASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PYRAZOLOSPIROCÉTONE ACÉTL-COA CARBOXYLASE
  申请人：PFIZER

  公开号：WO2009144554A1

  公开（公告）日：2009-12-03

  The invention provides compounds of Formula (1) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of acetyl-CoA carboxylase enzyme(s) in an animal.

  本发明提供了式(1)的化合物或所述化合物的药用可接受盐，其中R1、R2和R3如本文所述；其药物组合物；以及用于治疗通过抑制动物中的乙酰辅酶A羧化酶酶活性来调节的疾病、病症或障碍的使用方法。
• [EN] CHROMAN - SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS<br/>[FR] AMIDES DE PIPÉRIDINE SPIROCYCLIQUE CHROMANIQUE EN TANT QUE MODULATEURS DES CANAUX IONIQUES
  申请人：VERTEX PHARMA

  公开号：WO2012112743A1

  公开（公告）日：2012-08-23

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  这项发明涉及用于抑制离子通道的螺环色满烷酰胺衍生物。该发明还提供了包含本发明化合物的药用可接受组合物，以及使用这些组合物治疗各种疾病的方法。
• CHROMAN-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
  申请人：HADIDA-RUAH Sara Sabina

  公开号：US20120245136A1

  公开（公告）日：2012-09-27

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及一种用作离子通道抑制剂的色满环螺环己烷酰胺衍生物。本发明还提供了包括本发明化合物的药学上可接受的组合物，并提供了使用这些组合物治疗各种疾病的方法。
• Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors
  申请人：Corbett Jeffrey W.

  公开号：US20110028390A1

  公开（公告）日：2011-02-03

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

  本发明提供公式（1）的化合物或其药学上可接受的盐，其中R1，R2和R3如本文所述；其药物组合物；以及将其用于治疗动物中受乙酰辅酶A羧化酶酶抑制调节的疾病，状况或障碍。
• Chroman-spirocyclic piperidine amides as modulators of ion channels
  申请人：Hadida-Ruah Sara Sabina

  公开号：US10385070B2

  公开（公告）日：2019-08-20

  The invention relates to chroman spirocyclic piperidine amide derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及可用作离子通道抑制剂的铬螺环哌啶酰胺衍生物。本发明还提供了包含本发明化合物的药学上可接受的组合物，以及使用该组合物治疗各种疾病的方法。