Tert-butyl 3-[(4-hexoxyphenyl)carbamoyl]piperidine-1-carboxylate | 667455-91-6

• 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: Tert-butyl 3-[(4-hexoxyphenyl)carbamoyl]piperidine-1-carboxylate
• CAS: 667455-91-6
• 化学式: C₂₃H₃₆N₂O₄
• 分子量: 404.55
• InChiKey: XYVAIRZTUXNGFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Tert-butyl 3-[(4-hexoxyphenyl)carbamoyl]piperidine-1-carboxylate 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 16.0h， 生成 N-[4-(n-hexyloxy)phenyl]-N-methylamine
  参考文献：
  名称：

  Investigation of platelet aggregation inhibitory activity by phenyl amides and esters of piperidinecarboxylic acids

  摘要：

  A series of anilides and phenyl esters of piperidine-3-carboxylic acid (nipecotic acid) were synthesized and tested for the ability to inhibit aggregation of human platelet rich-plasma triggered by adenosine 5'-diphosphate (ADP) and adrenaline. As a rule, amides were about two times more active than the corresponding esters, and derivatives bearing substituents at the para position of the phenyl ring were significantly more active than the meta-substituted ones. Among the tested compounds, 4-hexyloxyanilide of nipecotic acid (18a) was found to be the most active one, its IC50 value being close to that of the most active bis-3-carbamoyl-piperidines reported in literature (ca. 40 muM) and aspirin (ca. 60 muM) in ADP- and adrenaline-induced aggregation, respectively. Compared with the isomeric 4-hexyloxyanilides of piperidine-2-carboxylic (pipecolinic) and piperidine-4-carboxylic (isonipecotic) acids, compound 18a showed higher activity, and a Hansch-type quantitative structure-activity relationship (QSAR) study highlighted lipophilicity and increase in electron density of the phenyl ring as the properties which mainly increase the antiplatelet activity (r(2) = 0.74, q(2) = 0.64). The interaction of nipecotoyl anilides with phosphatidylinositol, a major component of the inner layer of the platelet membranes, was investigated by means of flexible docking calculation methods to give an account of a key event underlying their biological action. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00599-0
• 作为产物：
  描述：

  对氨基苯酚 在 sodium hydride 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 Tert-butyl 3-[(4-hexoxyphenyl)carbamoyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Lipophilicity-related inhibition of blood platelet aggregation by nipecotic acid anilides

  摘要：

  Using N-[4-(hexyloxy)phenyl]piperidine-3-carboxamide (17c) as a structural lead, a number of isomers, derivatives, and ring-opened analogs were synthesized and tested for their ability to block the in vitro aggregation of human platelets induced by adenosine 5'-diphosphate (ADP). For the most active compounds, inhibition of the platelet aggregation triggered by arachidonic acid (AA) and ADP-induced intraplatelet calcium mobilization was also demonstrated. Based on quantitative structure-activity relationships (QSARs), we proved the impact of hydrophobicity on antiplatelet activity by a nonlinear (parabolic or bilinear) relationship between pIC(50) and lipophilicity, as assessed by RP-HPLC capacity factors and Clog P (i.e. calculated 1-octanol-water partition coefficients). This study highlighted the following additional SARs: quasi-isolipophilic isomers of 17c (isonipecotanilides and pipecolinanilides) and ring-opened analogs (e.g. anilide of beta-alanine) exhibited lower antiplatelet activity; methylation of the piperidine nitrogen of 17c has no effect, whereas alkylation with an n-propyl group decreases the activity by a factor of approximately 2, most likely due to a conformation-dependent decrease in lipophilicity. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.03.003