1-(1-Naphthylacetyl)-4-(pyridin-3-ylcyanomethyl)piperazine | 137074-08-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(1-Naphthylacetyl)-4-(pyridin-3-ylcyanomethyl)piperazine
• 英文别名: 1-(1-Naphthylacetyl)-4-(3-pyridylcyanomethyl)piperazine；[4-(2-Naphthalen-1-yl-acetyl)-piperazin-1-yl]-pyridin-3-yl-acetonitrile；2-[4-(2-naphthalen-1-ylacetyl)piperazin-1-yl]-2-pyridin-3-ylacetonitrile
• CAS: 137074-08-9
• 化学式: C₂₃H₂₂N₄O
• 分子量: 370.454
• InChiKey: VUJQACNUFSYVIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-萘乙酸 以75%的产率得到1-(1-Naphthylacetyl)-4-(pyridin-3-ylcyanomethyl)piperazine
  参考文献：
  名称：

  (cyanomethyl)pyridines useful as PAF antagonists

  摘要：

  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。

  公开号：

  EP0441226A1

文献信息

• (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.