5,8-二氮杂螺[3.5]壬烷 | 90566-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5,8-二氮杂螺[3.5]壬烷
• 英文名称: 5,8-diazaspiro<3.5>nonane
• 英文别名: 5,8-Diazaspiro[3.5]nonane
• CAS: 90566-57-7
• 化学式: C₇H₁₄N₂
• mdl: MFCD07373056
• 分子量: 126.202
• InChiKey: GGRDXGCQBQZPNZ-UHFFFAOYSA-N

物化性质

• 沸点：
  210.0±8.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5,8-二氮杂螺[3.5]壬烷 在 甲酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 20.0h， 生成 8-[(1R,3S)-6-chloro-3-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]-5-methyl-5,8-diazaspiro[3.5]nonane
  参考文献：
  名称：

  Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity

  摘要：

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.

  DOI：

  10.1021/jm00022a004
• 作为产物：
  描述：

  5,8-Diazaspiro[3.5]non-8-ene 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 5,8-二氮杂螺[3.5]壬烷
  参考文献：
  名称：

  Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity

  摘要：

  A study of the effect of aromatic substitution on D-1 and D-2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro- or B-fluoro-substituted derivatives show preference for D-1 receptors. D-1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D-1 and D-2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chlorosubstituted derivatives have potent D-1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED(50) values about 1 mu mol/kg. In vitro all compounds show preference for D-1 receptors, but in vivo they are equally effective as D-1 and D-2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha(1) adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being ''atypical'' antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D-2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D-1 receptor site.

  DOI：

  10.1021/jm00022a004

文献信息

• (Indazol-4-YL) Hexahydropyrrolopyrrolones and Methods of Use
  申请人：AbbVie Inc.

  公开号：US20160264582A1

  公开（公告）日：2016-09-15

  Compounds of formula (I) and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein G Ar , L 1 , Z 1 and Z 2 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by voltage-gated sodium channels, e.g., Na v 1.7 and/or Na v 1.8. Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

  式（I）的化合物及其药用可接受的盐、酯、酰胺或放射标记形式，其中G、Ar、L1、Z1和Z2如规范中所定义，可用于治疗由电压门控钠通道如Na v 1.7和/或Na v 1.8预防或改善的病症或紊乱。公开了制备这些化合物的方法。还公开了式（I）化合物的药物组合物，以及使用这些化合物和组合物的方法。
• [EN] HETEROARYL COMPOUNDS AND THEIR USE AS MER INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE MER
  申请人：DONG A SOCIO HOLDINGS CO LTD

  公开号：WO2018071343A1

  公开（公告）日：2018-04-19

  Compounds of formula (I) [Formula should be inserted here] and a pharmaceutically acceptable salt thereof, wherein A, R1, R2, R3, R4, R5, R6, R7, R24, X, L, n and p are as defined in the specification, are useful for treating or preventing Mer tyrosine kinase receptor modulated disease or conditions. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

  式(I)的化合物及其药学上可接受的盐，其中A、R1、R2、R3、R4、R5、R6、R7、R24、X、L、n和p如规范中定义的那样，可用于治疗或预防Mer酪氨酸激酶受体调节的疾病或症状。还描述了式(I)的化合物的药物组合物，以及使用这些化合物和组合物的方法。
• [EN] TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE<br/>[FR] INHIBITEURS, À BASE DE TRIAZOLOPYRIDINE, DE LA MYÉLOPEROXYDASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017040449A1

  公开（公告）日：2017-03-09

  The present invention provides compounds of Formula (I): wherein A is as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

  本发明提供了化合物的结构式（I）：其中A如规范中定义，并包括任何此类新化合物的组合物。这些化合物是髓过氧化物酶（MPO）抑制剂和/或嗜酸性粒细胞过氧化物酶（EPX）抑制剂，可用作药物。
• Indazole Ureas and Method of Use
  申请人：AbbVie Inc.

  公开号：US20160075692A1

  公开（公告）日：2016-03-17

  Compounds of formula (I) and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein A, R 1 and R 2 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by voltage-gated sodium channels, e.g., Na v 1.7 and/or Na v 1.8. Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

  化合物的化学式（I）及其药用可接受的盐、酯、酰胺或放射标记形式，其中A、R1和R2如规范中所定义，可用于治疗由电压门控钠通道如Na v 1.7和/或Na v 1.8预防或改善的疾病或疾病。公开了制备这些化合物的方法。还公开了化合物的药物组合物，以及使用这些化合物和组合物的方法。
• 6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
  申请人：SANOFI

  公开号：US20130150340A1

  公开（公告）日：2013-06-13

  The present invention relates to 1H-pyrazolo[3,4-b]pyridine compounds of the formula I, in which R 1 , R 2 , R 3 and R 4 are defined as indicated below. The compounds of the formula I are kinase inhibitors, and are useful for the treatment of diseases associated with diabetes and diabetic complications, such as, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy, for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式I的1H-吡唑并[3,4-b]吡啶化合物，其中R1、R2、R3和R4如下所示。式I的化合物是激酶抑制剂，对于治疗与糖尿病及糖尿病并发症相关的疾病，如糖尿病肾病、糖尿病神经病变和糖尿病视网膜病变等，具有用处。此外，本发明还涉及将式I的化合物用作药物中的活性成分，以及包含它们的药物组合物。