N-butyl-N-methylpyridine-3-carboxamide | 142566-02-7

• 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: N-butyl-N-methylpyridine-3-carboxamide
• 英文别名: N-Butyl-N-methylpyridine-3-carboxamide
• CAS: 142566-02-7
• 化学式: C₁₁H₁₆N₂O
• mdl: MFCD00462303
• 分子量: 192.261
• InChiKey: APGWAGCYMJWZAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-butyl-N-methylpyridine-3-carboxamide 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以92%的产率得到3-(N-n-butyl-N-methylaminomethyl)pyridine
  参考文献：
  名称：

  Pyrrolidine-modified and 6-substituted analogs of nicotine: A structure—affinity investigation

  摘要：

  Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs. This led to a subsequent investigation of related conformationally restricted derivatives of these analogs. The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands. Although none of the ring-opened analogs binds with higher affinity than (-)nicotine (K-i = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; K-i = 28 nM) binds with significant affinity. A conformationally restricted analog of 12a, N-methyl [2,7]naphthyridine 30b (K-i = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl. In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties. Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine. Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its pre presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity.

  DOI：

  10.1016/s0223-5234(97)89850-9
• 作为产物：
  描述：

  甲基丁胺 、 氯化烟碱盐酸盐 在 三乙胺 作用下， 以 氯仿 为溶剂， 以74%的产率得到N-butyl-N-methylpyridine-3-carboxamide
  参考文献：
  名称：

  Pyrrolidine-modified and 6-substituted analogs of nicotine: A structure—affinity investigation

  摘要：

  Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs. This led to a subsequent investigation of related conformationally restricted derivatives of these analogs. The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands. Although none of the ring-opened analogs binds with higher affinity than (-)nicotine (K-i = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; K-i = 28 nM) binds with significant affinity. A conformationally restricted analog of 12a, N-methyl [2,7]naphthyridine 30b (K-i = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl. In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties. Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine. Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its pre presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity.

  DOI：

  10.1016/s0223-5234(97)89850-9

文献信息

• Molecular determinants of the platelet aggregation inhibitory activity of carbamoylpiperidines
  作者：Zixia Feng、Ramachander Gollamudi、Elwood O. Dillingham、Stephen E. Bond、Beverly A. Lyman、William P. Purcell、Robert J. Hill、Walter A. Korfmacher

  DOI：10.1021/jm00094a004

  日期：1992.8

  Compound 3a was resolved into (+) and (-) enantiomers and a meso (0) diastereomer using fractional crystallization, diastereomeric tartrate formation, and chiral HPLC. Compared to (-)-3a, the (+) isomer was 15 times more potent when ADP was the agonist and 19 times more active when collagen was used as the agonist. Molecular modeling of R,R- and S,S-3a using the SYBYL program was used to examine their interactions

  合成了一系列的α，α′-双[3-（N，N-二烷基氨基甲酰基）哌啶子基]-对二甲苯，并测试了它们对ADP诱导的人血小板聚集的抑制活性。当将log 1 / C（活性）相对于log P（辛醇/水分配系数）作图时，可获得抛物线曲线。使用该模型作为模型，合成了新的类似物，α，α'-双-[3-（N-甲基-N-丁基氨基甲酰基）哌啶子基]-对二甲苯e（3g），预测的IC50为25 microM。随后评估该化合物时，IC50为22.1 +/- 5.5 microM，表明该模型的适用性。氨基甲酰基取代基的酰胺氧似乎是活性所必需的。因此，例如，当3a的酰胺羰基（IC 50 ＝44.5μM）还原成CH 2时，所得化合物4的活性大大降低，IC 50 ＝1565μM。使用分步结晶，酒石酸酯非对映异构体形成和手性HPLC，将化合物3a拆分为（+）和（-）对映异构体以及内消旋（0）非对映异构体。与（-）-3a相比，当AD
• Design and Synthesis of Piperidine-3-carboxamides as Human Platelet Aggregation Inhibitors
  作者：Xiaozhang Zheng、Somna R. Salgia、Walter B. Thompson、Elwood O. Dillingham、Stephen.E. Bond、Zixia Feng、K. Ram Prasad、Ram Gollamudi

  DOI：10.1021/jm00001a023

  日期：1995.1

  structure-activity analysis was carried out using eight 1-alkyl(aralkyl)nipecotamides (type 5), 33 bis-nipecotamidoalkanes and aralkanes (type 6), and 7 N,N'-bis(nipecotoyl)-piperazines (type 7) as inhibitors of human platelet aggregation. Steric factors played an important role in determining the activity of type 5 compounds possessing an an appropriate degree of hydrophobic character. Types 6 and 7 compounds were

  使用8种1-烷基（芳烷基）哌酰胺类（5型），33种双-邻酰胺基烷烃和芳烃（6类）和7种N，N'-双（苯甲酰基）-哌嗪（7类）进行了详细的结构活性分析）作为人类血小板聚集的抑制剂。立体因子在确定具有适当程度的疏水性的5型化合物的活性中起着重要作用。6型和7型化合物比相应的5型分子更有效。疏水特性似乎影响6型化合物的活性。哌啶环上的3-取代基对于抗血小板活性是必不可少的。取代基最好是酰胺，其C直接连接在环上。3,5-二取代和2-取代导致活性下降。当两个nipecotoyl环N原子通过一个芳烷基连接并相隔约7 A时，可获得最佳活性。这表明范德华力和pi相互作用可能决定抑制剂与血小板之间的相互作用。最有效的6型抑制剂是α，α'-双[3-（N-乙基-N-丁基氨基甲酰基）哌啶子基]-对二甲苯（6i）。最有效的5型化合物是1-癸基-3-（N，N-二乙基氨基甲酰基）哌啶（5a）。7型化合物哌嗪环上的任何取