1-((2-methyl-3-pyridyl)cyanomethyl)piperazine | 149691-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-((2-methyl-3-pyridyl)cyanomethyl)piperazine
• 英文别名: 1-[(2-methyl-pyridin-3-yl)cyanomethyl]piperazine；2-(2-Methylpyridin-3-yl)-2-piperazin-1-ylacetonitrile
• CAS: 149691-39-4
• 化学式: C₁₂H₁₆N₄
• mdl: MFCD24392541
• 分子量: 216.286
• InChiKey: XNXRIOPIUVEIHX-UHFFFAOYSA-N

物化性质

• 沸点：
  362.7±42.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 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：
  52
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((2-methyl-3-pyridyl)cyanomethyl)piperazine 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 1-(3-amino-3-phenylpropionyl)-4-[(2-methyl-pyridin-3-yl)cyanomethyl]piperazine
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists

  摘要：

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.

  DOI：

  10.1021/jm00072a019
• 作为产物：
  描述：

  1-(tert-butoxycarbonyl)-4-(cyanomethyl)-4-((2-pyridyl)methyl)piperazinium bromide 在 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 氯仿 、 乙腈 为溶剂， 反应 19.0h， 生成 1-((2-methyl-3-pyridyl)cyanomethyl)piperazine
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists

  摘要：

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.

  DOI：

  10.1021/jm00072a019

文献信息

• (2-Alkyl-3-pyridyl)methylpiperazine derivatives as PAF antagonists
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0528172A1

  公开（公告）日：1993-02-24

  The present invention relates to new (2-alkyl-3-pyridyl)methylpiperazine derivatives of general formula I: wherein R¹, R² and Z are as defined in Claim 1. The invention also relates to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent, orally active PAF antagonists and, consequently, they are useful in the treatment of the diseases in which this substance is involved.

  本发明涉及一般式I的新(2-烷基-3-吡啶基)甲基哌嗪衍生物，其中R¹，R²和Z如权利要求1所定义。该发明还涉及它们的制备方法以及含有它们的药物组合物。这些化合物是有效的口服PAF拮抗剂，因此它们在治疗涉及该物质的疾病中很有用。
• 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
• Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists
  作者：Elena Carceller、Manuel Merlos、Marta Giral、Carmen Almansa、Javier Bartroli、Julian Garcia-Rafanell、Javier Forn

  DOI：10.1021/jm00072a019

  日期：1993.10

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.