4-(3-piridylcyanomethyl)piperidine | 143816-99-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(3-piridylcyanomethyl)piperidine
• 英文别名: 4-(1-(3-Pyridyl)-cyanomethyl)piperidine；4-(pyridin-3-ylcyanomethyl)piperidine；4-(3-pyridylcyanomethyl)piperidine；2-Piperidin-4-yl-2-pyridin-3-ylacetonitrile
• CAS: 143816-99-3
• 化学式: C₁₂H₁₅N₃
• 分子量: 201.271
• InChiKey: SOKWBEYESXFSPB-UHFFFAOYSA-N

物化性质

• 沸点：
  383.4±27.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-二苯基乙酸 、 4-(3-piridylcyanomethyl)piperidine 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以45%的产率得到1-(diphenylacetyl)-4-(pyridin-3-ylcyanomethyl)piperidine
  参考文献：
  名称：

  (Pyridylcyanomethyl)piperazines as orally active PAF antagonists

  摘要：

  A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF-antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3-pyridylcyanomethyl)-piperazine, 1-acyl-4-(4-pyridylcyanomethyl)piperazine, 1-acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3-pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3-diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development.

  DOI：

  10.1021/jm00100a018
• 作为产物：
  描述：

  4-羟基哌啶-1-甲酸乙酯 在 三甲基氯硅烷 、 TEA 、 sodium hydride 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 66.17h， 生成 4-(3-piridylcyanomethyl)piperidine
  参考文献：
  名称：

  (Pyridylcyanomethyl)piperazines as orally active PAF antagonists

  摘要：

  A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF-antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3-pyridylcyanomethyl)-piperazine, 1-acyl-4-(4-pyridylcyanomethyl)piperazine, 1-acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3-pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3-diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development.

  DOI：

  10.1021/jm00100a018

文献信息

• (cyanomethyl)pyridines useful as PAF antagonists
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0441226A1

  公开（公告）日：1991-08-14

  57 The present invention relates to new (cyanomethyl)pyridines of general formula I: wherein A is nitrogen and B is -CH-, or B is nitrogen and A is -CH-; the group Y-W- represents a group of formula N-CR1(CN)-, N-CH2-CH(CN)-, CH-CH(CN)- or C=C(CN)- wherein R1 is hydrogen or a C1-C6 alkyl group; R represents a group of formula R2CO-, R3R4N-(CH2)nCO- or R5-(CH2)m wherein R2 represents C1-C15 alkyl, aryl, aryl-(C1-C6)-alkyl, aryl-(C1-C6)-alkenyl, diaryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkenyl, arylhydroxy-(C1-C6)-alkyl, diarylhydroxy-(Ci-C6)-alkyl, aryl-(C1-C6)-alkoxy, diaryl-(C1-C6)-alkoxy, or heteroaryl-(C1-C6)-alkyl group; n is 0, 1, 2 or 3; R3 is hydrogen, C1-C6 alkyl, aryl or aryl-(Cl-C6)-alkyl group; R4 is C3-C6 cycloalkyl, aryl, aryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkyl, aryl-(C1-C6)-alkylcarbonyl or diaryl-(C1-C6)-alkylcarbonyl group; m is 0, 1 or 2; and R5 is aryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkyl, diaryl-(C1-C6)-alkylcarbonylamino or diaryl-(C1-C6)-alkylaminocarbonyl group. These compounds are potent, orally active PAF antagonists and consequently, useful in the treatment of the diseases in which this substance is involved.

  本发明涉及一般式I的新(氰甲基)吡啶：其中A为氮，B为-CH-，或者B为氮，A为-CH-；基团Y-W-表示一种具有以下式N-CR1(CN)-、N-CH2-CH(CN)-、CH-CH(CN)-或C=C(CN)-的基团，其中R1为氢或C1-C6烷基；R表示一种具有以下式R2CO-、R3R4N-(CH2)nCO-或R5-(CH2)m的基团，其中R2表示C1-C15烷基、芳基、芳基-(C1-C6)-烷基、芳基-(C1-C6)-烯基、二芳基-(C1-C6)-烷基、二芳基-(C1-C6)-烯基、芳基羟基-(C1-C6)-烷基、二芳基羟基-(Ci-C6)-烷基、芳基-(C1-C6)-氧基、二芳基-(C1-C6)-氧基或杂芳基-(C1-C6)-烷基；n为0、1、2或3；R3为氢、C1-C6烷基、芳基或芳基-(Cl-C6)-烷基；R4为C3-C6环烷基、芳基、芳基-(C1-C6)-烷基、二芳基-(C1-C6)-烷基、芳基-(C1-C6)-烷基羰基或二芳基-(C1-C6)-烷基羰基；m为0、1或2；R5为芳基-(C1-C6)-烷基、二芳基-(C1-C6)-烷基、二芳基-(C1-C6)-烷基羰胺基或二芳基-(C1-C6)-烷基氨基羰基基团。这些化合物是有效的口服PAF拮抗剂，因此，在这种物质参与的疾病治疗中非常有用。
• Cyanomethylpyridine derivatives as PAF antagonists and 5-lipoxygenase inhibitors
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0617032A1

  公开（公告）日：1994-09-28

  The present invention relates to new cyanomethylpyridine derivatives of formula I wherein Y represents N or CH; R₁ represents fluoro or chloro; R₂ represents hydrogen or C₁₋₄ alkyl; m is 0, 1 or 2; n is 0 or 1; p is 0 or 1; A represents a covalent bond or a group of formula -CONHCH(Ar)-, -NHCH(Ar)-, -SO₂NHCH(Ar)-, -NHCONHCH(Ar)- or -OC(=O)NHCH(Ar)-, and when p is 1, A can also represent -CH(Ar)NH-; and Ar represents phenyl or phenyl substituted with one or more groups chosen from halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy or trifluoromethyl. These compounds are PAF antagonist and/or 5-lipoxygenase inhibitors.

  本发明涉及式 I 的新氰基甲基吡啶衍生物 其中 Y 代表 N 或 CH；R₁ 代表氟或氯；R₂ 代表氢或 C₁₋₄ 烷基；m 为 0、1 或 2；n 为 0 或 1；p 为 0 或 1；A 代表共价键或-CONHCH(Ar)-、-NHCH(Ar)-、-SO₂NHCH(Ar)-、-NHCONHCH(Ar)- 或-OC(=O)NHCH(Ar)-式中的基团，当 p 为 1 时，A 也可以代表-CH(Ar)NH-；Ar 代表苯基或被一个或多个基团取代的苯基，这些基团选自卤素、C₁₋₄ 烷基、C₁₋₄ 烷氧基或三氟甲基。这些化合物是 PAF 拮抗剂和/或 5-脂氧合酶抑制剂。
• US5420131A
  申请人：——

  公开号：US5420131A

  公开（公告）日：1995-05-30
• (Pyridylcyanomethyl)piperazines as orally active PAF antagonists
  作者：Elena Carceller、Carmen Almansa、Manuel Merlos、Marta Giral、Javier Bartroli、Julian Garcia-Rafanell、Javier Forn

  DOI：10.1021/jm00100a018

  日期：1992.10

  A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF-antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3-pyridylcyanomethyl)-piperazine, 1-acyl-4-(4-pyridylcyanomethyl)piperazine, 1-acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3-pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3-diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development.