rac-8-(2-Oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one | 857873-63-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: rac-8-(2-Oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one
• 英文别名: 8-(2-Oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one；8-(2-oxocyclohexyl)-4-phenyl-2,8-diazaspiro[4.5]decan-1-one
• CAS: 857873-63-3
• 化学式: C₂₀H₂₆N₂O₂
• 分子量: 326.439
• InChiKey: LLPBKPGIPSLCAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-8-(2-Oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one 、 间溴苯甲醚 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 8-[(1R,2R)-2-Hydroxy-2-(3-methoxy-phenyl)-cyclohexyl]-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one
  参考文献：
  名称：

  Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability

  摘要：

  A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin/Orphanin FQ peptide (NOP) receptor. In particular these novel compounds 4 as well as the 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one 3 show improved metabolic stability and pharmacokinetic profiles in rodents compared to previous triazaspiropiperidine series 1 and 2. We have also identified within these diazaspiropiperidine series a key relationship between reducing basicity of the piperidine nitrogen and reducing hERG affinity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.058
• 作为产物：
  描述：

  rac-8-(2-hydroxy-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one 在 pyridine-SO3 complex 、 TEA 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 rac-8-(2-Oxo-cyclohexyl)-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one
  参考文献：
  名称：

  Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability

  摘要：

  A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin/Orphanin FQ peptide (NOP) receptor. In particular these novel compounds 4 as well as the 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one 3 show improved metabolic stability and pharmacokinetic profiles in rodents compared to previous triazaspiropiperidine series 1 and 2. We have also identified within these diazaspiropiperidine series a key relationship between reducing basicity of the piperidine nitrogen and reducing hERG affinity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.058

文献信息

• Diaza-spiropiperidine derivatives
  申请人：Ceccarelli Maria Simona

  公开号：US20050154001A1

  公开（公告）日：2005-07-14

  The present invention relates to compounds of formula wherein A-B is —CH 2 —CH 2 —, —CH 2 —O— or —O—CH 2 —; X is hydrogen or hydroxy; R 1 is aryl, optionally substituted by one or two substituents selected from the group consisting of halogen, lower alkyl, cyano, CF 3 , —OCF 3 , lower alkoxy, —SO 2 -lower alkyl and heteroaryl; R 2 is aryl, optionally substituted by one or two substituents selected from the group consisting of halogen, lower alkyl, CF 3 , and lower alkoxy; R 3 is hydrogen or lower alkyl; n is 0, 1 or 2; or a pharmaceutically active salt thereof. The compounds of the invention may be used in the treatment of neurological and neuropsychiatric disorders.

  本发明涉及以下结构的化合物 其中 A-B为—CH 2 —CH 2 —, —CH 2 —O—或—O—CH 2 —; X为氢或羟基; R 1 为芳基，可选地由卤素、较低烷基、氰基、CF 3 、—OCF 3 、较低烷氧基、—SO 2 -较低烷基和杂环芳基中选择的一种或两种取代基取代; R 2 为芳基，可选地由卤素、较低烷基、CF 3 和较低烷氧基中选择的一种或两种取代基取代; R 3 为氢或较低烷基; n为 0, 1 或 2; 或其药用活性盐。本发明的化合物可用于治疗神经和神经精神疾病。
• DIAZA-SPIROPIPERIDINE DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1720873A1

  公开（公告）日：2006-11-15
• US7173133B2
  申请人：——

  公开号：US7173133B2

  公开（公告）日：2007-02-06
• [EN] DIAZA-SPIROPIPERIDINE DERIVATIVES<br/>[FR] DERIVES DIAZA-SPIROPIPERIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005068463A1

  公开（公告）日：2005-07-28

  The present invention relates to compounds of formula (I); wherein A-B is -CH2-CH2-, -CH2-O- or -O-CH2-; X is hydrogen or hydroxy; Rl is aryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, lower alkyl, cyano, CF3, -OCF3, lower alkoxy, -SO2-lower alkyl or by heteroaryl, R2 is aryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, lower alkyl, CF3 or lower alkoxy; R3 is hydrogen or lower alkyl; n is 0, 1 or 2; and to their pharmaceutically active salts. The compounds of formula I may be used in the treatment of neurological and neuropsychiatric disorders.
• Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability
  作者：Daniela Alberati、Dominik Hainzl、Synèse Jolidon、Eva A. Krafft、Anke Kurt、Axel Maier、Emmanuel Pinard、Andrew W. Thomas、Daniel Zimmerli

  DOI：10.1016/j.bmcl.2006.05.058

  日期：2006.8

  A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin/Orphanin FQ peptide (NOP) receptor. In particular these novel compounds 4 as well as the 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one 3 show improved metabolic stability and pharmacokinetic profiles in rodents compared to previous triazaspiropiperidine series 1 and 2. We have also identified within these diazaspiropiperidine series a key relationship between reducing basicity of the piperidine nitrogen and reducing hERG affinity. (c) 2006 Elsevier Ltd. All rights reserved.