4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzonitrile | 79421-39-9

• 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: 4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzonitrile
• 英文别名: 4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)benzonitrile；4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzonitrile；1-(4-Cyanophenyl)-4-piperidone ethylene acetal；4-(8-aza-1,4-dioxaspiro[4,5]dec-8-yl)benzonitrile；4-(8-aza-1,4-dioxaspiro[4.5]dec-8-yl)benzonitrile
• CAS: 79421-39-9
• 化学式: C₁₄H₁₆N₂O₂
• mdl: MFCD19374290
• 分子量: 244.293
• InChiKey: FGMYNGSWRAOYSV-UHFFFAOYSA-N

物化性质

• 熔点：
  135.5-135.9 °C
• 沸点：
  437.0±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzonitrile 在 sodium hydroxide 作用下， 以 盐酸 、 乙醇 为溶剂， 以41%的产率得到4-(4-oxo-piperidin-1-yl)-benzoic acid
  参考文献：
  名称：

  Combination of a selective 5-HT.sub.1A antagonist and a selective ub

  摘要：

  该发明涉及第一组分(a)和第二组分(b)的组合物。第一组分(a)是一种选择性5-HT.sub.1A受体拮抗剂，具有式I，其中R.sub.1为正丙基或环丁基，R.sub.2为异丙基、叔丁基、环丁基、环戊基或环己基，R.sub.3为氢，R.sub.4为氢或甲基，并且为(R)-对映体形式。第二组分(b)是一种选择性h5-HT.sub.1B受体拮抗剂或部分激动剂，具有式II，其中X为CH.sub.2、O，Y为CONH、NHCO，R.sub.1为H、C.sub.1 -C.sub.6烷基、C.sub.3 -C.sub.6环烷基，R.sub.2为H、C.sub.1 -C.sub.6烷基、C.sub.1 -C.sub.6烷氧基、卤素，R.sub.3为，R.sub.4和R.sub.5独立地为H或C.sub.1 -C.sub.4烷基，为消旋体、R-对映体或S-对映体，所述组分(a)和(b)为自由碱、溶剂合物或其药学上可接受的盐形式，其制备方法，含有该组合物的药物配方，使用该组合物治疗情感障碍如抑郁症、焦虑症和强迫症的方法，以及含有该组合物的试剂盒。

  公开号：

  US06159972A1
• 作为产物：
  描述：

  对氟苯腈 、 4-哌啶酮缩乙二醇 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙酸乙酯 为溶剂， 以79%的产率得到4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzonitrile
  参考文献：
  名称：

  Substituted (aminoiminomethyl or aminomethyl) benzoheteroaryl compounds

  摘要：

  这项发明涉及一种化合物，其化学式为I，该化合物是(aminoiminomethyl或aminomethyl)benzoheteroaryl化合物，可通过将该化合物与含有凝血因子Xa的组合物结合来抑制凝血因子Xa的活性。本发明还涉及含有化合物I的组合物、其制备方法以及它们的用途，如用于抑制凝血酶的形成或用于治疗患有与生理上有害的凝血酶过量相关的疾病状态的患者。

  公开号：

  US06541505B1

文献信息

• Substituted 1,2,3,4-tetrahydronaphthalene derivatives
  申请人：Astra Aktiebolag

  公开号：US06124283A1

  公开（公告）日：2000-09-26

  New piperidinyl- or piperazinyl-substituted-1,2,3,4-tetrahydronaphthalene derivatives having the formula ##STR1## wherein X is N or CH; Y is NR.sub.2 CH.sub.2, CH.sub.2 --NR.sub.2, NR.sub.2 --CO, CO--NR.sub.2 or NR.sub.2 SO.sub.2 ; R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 cycloalkyl; R.sub.3 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or (CH.sub.2).sub.n -aryl, where aryl is phenyl or a heteroaromatic ring containing one or two heteroatoms selected from N, O and S and which may be mono- or di-substituted; n is 0-4; as (R)-enantiomer, (S)-enantiomer or a racemate in the form of the free base or a pharmaceutically acceptable salt or hydrate thereof; a pharmaceutical formulation containing the compounds, use of the compounds in the treatment of 5-hydroxytryptamine mediated disorders, processes for the preparation of the compounds and intermediates for the preparation of the compounds.

  新的哌啶基或哌嗪基取代的1,2,3,4-四氢萘衍生物具有以下结构式：##STR1## 其中X为N或CH；Y为NR.sub.2 CH.sub.2，CH.sub.2--NR.sub.2，NR.sub.2--CO，CO--NR.sub.2或NR.sub.2 SO.sub.2；R.sub.1为H，C.sub.1-C.sub.6烷基或C.sub.3-C.sub.6环烷基；R.sub.3为C.sub.1-C.sub.6烷基，C.sub.3-C.sub.6环烷基或(CH.sub.2).sub.n-芳基，其中芳基为苯基或含有N、O和S中的一个或两个杂原子的杂芳环，可以是单取代或双取代；n为0-4；作为(R)-对映体，(S)-对映体或自由碱形式或其药学上可接受的盐或水合物的混合物；含有这些化合物的药物配方，这些化合物在治疗5-羟色胺介导的疾病中的用途，制备这些化合物的方法以及制备这些化合物的中间体。
• Combination of a 5-HT reuptake inhibitor and a H5-HT1B anatagonist or
  申请人：Astrazeneca AB

  公开号：US06159971A1

  公开（公告）日：2000-12-12

  The invention relates to a combination of a first component (a) which is a 5-HT reuptake inhibitor and a second component (b) which is selective h5-HT.sub.1B antagonist or partial agonist having the formula I ##STR1## wherein X is CH.sub.2, O; Y is CONH, NHCO; R.sub.1 is H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl; R.sub.2 is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, halogen; R.sub.3 is ##STR2## R.sub.4 and R.sub.5 independently are H or C.sub.1 -C.sub.4 alkyl, as racemate, R-enantiomer or S-enantiomer, and said components (a) and (b) being in the form of free bases, solvents or pharmaceutically acceptable salts thereof, the preparation thereof, pharmaceutical formulations containing said combination, use of and method of treatment of affective disorders such as depression, anxiety and OCD with said combination as well as a kit containing said combination.

  该发明涉及第一组分(a)为5-HT再摄取抑制剂和第二组分(b)为选择性h5-HT.sub.1B拮抗剂或部分激动剂的组合物，其具有以下式I的结构：其中X为CH.sub.2，O；Y为CONH，NHCO；R.sub.1为H，C.sub.1 -C.sub.6烷基，C.sub.3 -C.sub.6环烷基；R.sub.2为H，C.sub.1 -C.sub.6烷基，C.sub.1 -C.sub.6烷氧基，卤素；R.sub.3为##STR2## R.sub.4和R.sub.5独立地为H或C.sub.1 -C.sub.4烷基，作为拉丁酸酯、R-对映体或S-对映体，所述组分(a)和(b)以其自由碱、溶剂或药学上可接受的盐的形式存在，其制备方法，含有该组合物的药物配方，使用该组合物治疗情感障碍如抑郁症、焦虑症和强迫症的方法，以及含有该组合物的工具包。
• Combination of a selective 5-HT.sub.1A antagonist and a selective ub
  申请人：AstraZeneca AB

  公开号：US06159972A1

  公开（公告）日：2000-12-12

  The invention relates to a combination of a first component (a) which is a selective 5-HT.sub.1A receptor antagonist having the formula I wherein R.sub.1 is n-propyl or cyclobutyl, R.sub.2 is isopropyl, tertiary butyl, cyclobutyl, cyclopentyl or cyclohexyl, R.sub.3 is hydrogen and R.sub.4 is hydrogen or methyl and being in the (R)-enantiomer form, with a second component (b) which is a selective h5-HT.sub.1B antagonist or partial agonist having the formula II ##STR1## wherein X is CH.sub.2, O, Y is CONH, NHCO, R.sub.1 is H, C.sub.1 -C.sub.6 alky, C.sub.3 -C.sub.6 cycloalkyl, R.sub.2 is H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, halogen, R.sub.3 is ##STR2## R.sub.4 and R.sub.5 independently are H or C.sub.1 -C.sub.4 alkyl as racemate, R-enantiomer or S-enantiomer, and said components (a) and (b) being in the form of free bases, solvates or pharmaceutically acceptable salts thereof, the preparation thereof, pharmaceutical formulations containing said combination, use of and method of treatment of affective disorders such as depression, anxiety and OCD with said combination as well as a kit containing said combination.

  该发明涉及第一组分(a)和第二组分(b)的组合物。第一组分(a)是一种选择性5-HT.sub.1A受体拮抗剂，具有式I，其中R.sub.1为正丙基或环丁基，R.sub.2为异丙基、叔丁基、环丁基、环戊基或环己基，R.sub.3为氢，R.sub.4为氢或甲基，并且为(R)-对映体形式。第二组分(b)是一种选择性h5-HT.sub.1B受体拮抗剂或部分激动剂，具有式II，其中X为CH.sub.2、O，Y为CONH、NHCO，R.sub.1为H、C.sub.1 -C.sub.6烷基、C.sub.3 -C.sub.6环烷基，R.sub.2为H、C.sub.1 -C.sub.6烷基、C.sub.1 -C.sub.6烷氧基、卤素，R.sub.3为，R.sub.4和R.sub.5独立地为H或C.sub.1 -C.sub.4烷基，为消旋体、R-对映体或S-对映体，所述组分(a)和(b)为自由碱、溶剂合物或其药学上可接受的盐形式，其制备方法，含有该组合物的药物配方，使用该组合物治疗情感障碍如抑郁症、焦虑症和强迫症的方法，以及含有该组合物的试剂盒。
• Substituted (aminoiminomethyl or aminomethyl) benzoheteroaryl compounds
  申请人：Aventis Pharmaceuticals Inc.

  公开号：US06541505B1

  公开（公告）日：2003-04-01

  This invention is directed to an (aminoiminomethyl or aminomethyl)benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.

  这项发明涉及一种化合物，其化学式为I，该化合物是(aminoiminomethyl或aminomethyl)benzoheteroaryl化合物，可通过将该化合物与含有凝血因子Xa的组合物结合来抑制凝血因子Xa的活性。本发明还涉及含有化合物I的组合物、其制备方法以及它们的用途，如用于抑制凝血酶的形成或用于治疗患有与生理上有害的凝血酶过量相关的疾病状态的患者。
• An improved synthesis of N-aryl and N-heteroaryl substituted piperidones
  作者：Uwe Schön、Josef Messinger、M. Buckendahl、M.S. Prabhu、A. Konda

  DOI：10.1016/j.tetlet.2007.02.053

  日期：2007.4

  An efficient Pd(0)-catalyzed protocol for the rapid and efficient preparation of N-aryl and N-heteroaryl substituted piperidones is described. The two step syntheses proceed with an overall yield of 50–70% using X-Phos as optimal ligand for the Pd(0)-catalyzed Buchwald–Hartwig amination followed by subsequent hydrolysis of resulted ketals.

  描述了一种快速有效制备N-芳基和N-杂芳基取代的哌啶酮的有效Pd（0）催化方案。使用X-Phos作为Pd（0）催化的Buchwald-Hartwig胺化反应的最佳配体，两步合成的总产率为50-70％，随后水解生成的缩酮。