rac-3-(1-oxo-4-phenyl-2,8-diaza-spiro[4.5]dec-8-yl)-tetrahydro-pyran-4-carbonitrile | 857681-19-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: rac-3-(1-oxo-4-phenyl-2,8-diaza-spiro[4.5]dec-8-yl)-tetrahydro-pyran-4-carbonitrile
• 英文别名: 3-(1-Oxo-4-phenyl-2,8-diazaspiro[4.5]decan-8-yl)oxane-3-carbonitrile
• CAS: 857681-19-7
• 化学式: C₂₀H₂₅N₃O₂
• 分子量: 339.437
• InChiKey: JKKRPTPTSNIOAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 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：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  rac-3-(1-oxo-4-phenyl-2,8-diaza-spiro[4.5]dec-8-yl)-tetrahydro-pyran-4-carbonitrile 、 phenylmagnesium bromide 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 rac-4-phenyl-8-(3-phenyl-tetrahydropyran-4-yl)-2,8-diaza-spiro[4.5]decan-1-one
  参考文献：
  名称：

  4-Substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with superior pharmacological and pharmacokinetic parameters

  摘要：

  A novel class of 4-substituted-8-(1-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 g opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. These molecules also exhibit superior pharmacological and pharmacokinetic parameters, relative to all GlyT1 inhibitors of the spiropiperidine family, culminating in the identification of 16b with an oral bioavailability of similar to 60%. In addition, a straightforward two-step procedure for the assembly of the target molecules is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.063
• 作为产物：
  描述：

  四氢-2H-吡喃-3-酮 、 三甲基氰硅烷 、 1-phenyl-3,8-diazaspiro<4,5>decanone-4 在 溶剂黄146 作用下， 反应 1.0h， 生成 rac-3-(1-oxo-4-phenyl-2,8-diaza-spiro[4.5]dec-8-yl)-tetrahydro-pyran-4-carbonitrile
  参考文献：
  名称：

  4-Substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with superior pharmacological and pharmacokinetic parameters

  摘要：

  A novel class of 4-substituted-8-(1-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 g opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. These molecules also exhibit superior pharmacological and pharmacokinetic parameters, relative to all GlyT1 inhibitors of the spiropiperidine family, culminating in the identification of 16b with an oral bioavailability of similar to 60%. In addition, a straightforward two-step procedure for the assembly of the target molecules is also presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.063

文献信息

• Diaza-spiropiperidine derivatives
  申请人：Jolidon Synese

  公开号：US20050154000A1

  公开（公告）日：2005-07-14

  The present invention relates to compounds of formula wherein A—B, R 1 , R 2 , R 3 , R 4 , and n are as defined herein; and to pharmaceutically acceptable salts thereof. The compounds of formula I may be used in the treatment of neurological and neuropsychiatric disorders.

  本发明涉及以下式的化合物 其中 A—B，R 1 ，R 2 ， R 3 ，R 4 和n如本文所定义；以及其药学上可接受的盐。 式I的化合物可用于治疗神经系统和神经精神疾病。
• DIAZA-SPIROPIPERIDINE DERIVATIVES AS INHIBITORS OF GLYCINE TRANSPORTER 1 AND GLYCINE TRANSPORTER 2
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1716147B1

  公开（公告）日：2007-11-14
• US7265126B2
  申请人：——

  公开号：US7265126B2

  公开（公告）日：2007-09-04
• [EN] DIAZA-SPIROPIPERIDINE DERIVATIVES AS INHIBITORS OF TRANSPORTER 1 AND GLYCINE TRANSPORTER 2<br/>[FR] DERIVES DE LA DIAZA-SPIROPIPERIDINE UTILISES COMME INHIBITEURS DU TRANSPORTEUR 1 ET DU TRANSPORTEUR DE LA GLYCINE 2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005068462A1

  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-, O-CH2, CH2-S, -S-CH2-, CH2-C(O)-, C(O)-CH2-, .-N(R4)-CH2- or -CH2-N(R4)-; R1 is lower alkyl, lower alkenyl, cycloalkyl, or is aryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, cyano, lower alkyl, CF3, OCF3 or lower alkoxy, or is heteroaryl, optionally substituted by one or two substituents selected from the group consisting of halogen, lower alkyl, CF3 or lower alkoxy; R2 is lower alkyl, cycloalkyl, or is aryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, lower alkyl, CF3, lower alkoxy, or is heteroaryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, lower alkyl, CF3, lower alkoxy, or is heteroaryl, optionally substituted by one or two substituents, selected from the group consisting of halogen, lower alkyl, CF3, or lower alkoxy; R3 is hydrogen, lower alkyl or benzyl; R4 is hydrogen or benzyl; n is 0, 1 or 2; and to pharmaceutically available salts thereof. The compounds of formula I may be used in the treatment of neurological and neuropsychiatric disorders.