(2R)-4-(二(丙-2-基)氨基)-2-苯基-2-吡啶-2-基丁酰胺 | 74464-83-8

• 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
• 中文名称: (2R)-4-(二(丙-2-基)氨基)-2-苯基-2-吡啶-2-基丁酰胺
• 英文名称: (-)-Disopyramide
• 英文别名: (2R)-(-)-disopyramide；(R)-(+)-disopyramide；R-(-)-disopyramide；R(-)-disopyramide；(R)-disopyramide；R-disopyramide；2-Pyridineacetamide, alpha-(2-(bis(1-methylethyl)amino)ethyl)-alpha-phenyl-, (R)-；(2R)-4-[di(propan-2-yl)amino]-2-phenyl-2-pyridin-2-ylbutanamide
• CAS: 74464-83-8
• 化学式: C₂₁H₂₉N₃O
• 分子量: 339.481
• InChiKey: UVTNFZQICZKOEM-OAQYLSRUSA-N

物化性质

• 熔点：
  83-85 °C
• 沸点：
  505.2±50.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R)-4-(二(丙-2-基)氨基)-2-苯基-2-吡啶-2-基丁酰胺 在 potassium carbonate 、 间氯过氧苯甲酸 、 锌 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 1.0h， 生成 (-)-Mono-N-Desisopropyldisopyramide
  参考文献：
  名称：

  Synthesis and anticholinergic properties of the enantiomers of 4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide, the mono-N-dealkylated metabolite of disopyramide

  摘要：

  The 2R and 2S enantiomers of 4-isopropyl-2-(2-pyridyl)-2-phenylbutyramide [(2R)-2 and (2S)-2] were prepared from the respective 2R and 2S enantiomers of disopyramide [(2R)-1 and (2S)-1] by oxidation with peracid, Cope elimination, and subsequent zinc/HCl reduction of the resulting hydroxylamines (2R)-3 and (2S)-3. The enantiomers were tested as antagonists to the contraction of guinea pig ileum longitudinal muscle produced in response to electrically stimulated release of acetylcholine. The enantiomers showed IC50 values of 5.0 X 10(-6) and 14 X 10(-6) M for (2S)-2 and (2R)-2 respectively, about a 3-fold difference between enantiomers. Data are presented showing direct antagonism of acetylcholine in the guinea pig ileum assay. In a comparison of the anticholinergic effects of 2 and 1, the metabolite (2) was slightly less potent than disopyramide (1).

  DOI：

  10.1021/jm00137a024
• 作为产物：
  描述：

  达舒平 生成 (2R)-4-(二(丙-2-基)氨基)-2-苯基-2-吡啶-2-基丁酰胺
  参考文献：
  名称：

  二吡amide酰胺，4-（二异丙基氨基）-2-（2-吡啶基）-2-苯基丁酰胺的对映异构体的拆分，绝对构型和抗心律不齐特性。

  摘要：

  通过从甲醇-丙酮中分步结晶其非对映体酒石酸氢盐来拆分二吡op酰胺。由（+）-樟脑10磺酰氯制备的非对映体磺酰胺和通过LiAlH4还原拆分的碱获得的伯胺可通过高效液相色谱分离，并用于证明在实验误差范围内二吡甲酰胺的拆分完全。绝对构型通过X射线晶体学确定。（+）-[（（2R）-（-）-4-（二异丙基氨基）-2-（2-吡啶基）-2-苯基丁酰胺（+）-（2R，3R）-酒石酸氢盐]在空间群P212121中结晶： 14.789（4），b = 18.151（4），c = 9.878（2）A；Z = 4：Dx = 1.225，Dm（浮选C6H6 / CCl4）= 1.226 g cm-3。该结构通过直接方法解决。测试了对映体酒石酸氢盐的抗心律不齐特性。对映体酒石酸氢盐在延长兔脑室的有效不应期（ERP）方面同样有效。在3 x 10（-6）M时，[-（-）-酒石酸[来自（2S）-（+）-二吡酰胺]使ERP增加21

  DOI：

  10.1021/jm00183a015

文献信息

• Characteristic and complementary chiral recognition ability of four recently developed immobilized chiral stationary phases based on amylose and cellulose phenyl carbamates and benzoates
  作者：Takafumi Onishi、Takunori Ueda、Kenichi Yoshida、Kosuke Uosaki、Hiroyuki Ando、Ryota Hamasaki、Atsushi Ohnishi

  DOI：10.1002/chir.23446

  日期：2022.7

  various immobilized chiral stationary phases (CSPs) have been developed. The immobilized CSPs have opened up possibilities not only maintaining the high chiral recognition abilities as well as corresponding coated ones but also affording high durability to various mobile phase. This report directed to investigate enantioseparation of recently launched four immobilized CSPs with cellulose and amylose

  迄今为止，已经开发了各种固定化手性固定相 (CSP)。固定化的 CSP 不仅为保持高手性识别能力和相应的涂层能力开辟了可能性，而且为各种流动相提供了高耐久性。本报告旨在研究在正相液相色谱条件下最近推出的四种具有纤维素和直链淀粉骨架的固定化 CSP 的对映体分离。将它们的手性识别能力与之前开发的六种固定化 CSP 进行了比较。特别是，我们专注于手性识别的互补性。其中，直链淀粉三（3-氯-5-甲基苯基氨基甲酸酯）CSP，即CHIRALPAK IG，对各种外消旋体显示出显着的手性识别能力。正如预期的那样，研究的固定化 CSP 对各种流动相具有显着的耐久性，而相应的涂层 CSP 由于不可逆的降解而无法运行。利用不受限制的溶剂相容性，一些外消旋体的手性分离选择性得到改善。
• Substituted 5-phenyl-5-(aminoalkyl)-1,3-diazabicyclo[4.4.0]decan-4-ones
  申请人：G. D. Searle & Co.

  公开号：US04560754A1

  公开（公告）日：1985-12-24

  This invention relates to 5-(substituted phenyl)-5-[(substituted amino)alkyl]-1,3-diazabicyclo[4.4.0]decan-4-ones and 5-(substituted phenyl)-5-[(substituted amino)-alkyl]-1,3-diazabicyclo[4.4.0]dec-2-en-4-ones that are useful as antiarrhythmic agents.

  该发明涉及用作抗心律失常药物的5-(取代苯基)-5-[(取代氨基)烷基]-1,3-二氮杂双环[4.4.0]癸烷-4-酮和5-(取代苯基)-5-[(取代氨基)烷基]-1,3-二氮杂双环[4.4.0]癸-2-烯-4-酮。
• NELSON, W. L.;SNEED, CH. K.;GIACOMINI, K. M.;GIACOMINI, J. C.;STAUSS, J.;+, J. MED. CHEM., 1981, 24, N 5, 614-617
  作者：NELSON, W. L.、SNEED, CH. K.、GIACOMINI, K. M.、GIACOMINI, J. C.、STAUSS, J.、+

  DOI：——

  日期：——
• LE, CORRE PASCAL;GIBASSIER, DENIS;SADO, PIERRE;LE, VERGE ROGER, J. CHROMATOGR., 450,(1988) N 2, C. 211-216
  作者：LE, CORRE PASCAL、GIBASSIER, DENIS、SADO, PIERRE、LE, VERGE ROGER

  DOI：——

  日期：——
• Synthesis and anticholinergic properties of the enantiomers of 4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide, the mono-N-dealkylated metabolite of disopyramide
  作者：Wendel L. Nelson、Cherilyn K. Sneed、Kathleen M. Giacomini、John C. Giacomini、John Stauss、Terrence F. Blaschke、Brian M. Cox

  DOI：10.1021/jm00137a024

  日期：1981.5

  The 2R and 2S enantiomers of 4-isopropyl-2-(2-pyridyl)-2-phenylbutyramide [(2R)-2 and (2S)-2] were prepared from the respective 2R and 2S enantiomers of disopyramide [(2R)-1 and (2S)-1] by oxidation with peracid, Cope elimination, and subsequent zinc/HCl reduction of the resulting hydroxylamines (2R)-3 and (2S)-3. The enantiomers were tested as antagonists to the contraction of guinea pig ileum longitudinal muscle produced in response to electrically stimulated release of acetylcholine. The enantiomers showed IC50 values of 5.0 X 10(-6) and 14 X 10(-6) M for (2S)-2 and (2R)-2 respectively, about a 3-fold difference between enantiomers. Data are presented showing direct antagonism of acetylcholine in the guinea pig ileum assay. In a comparison of the anticholinergic effects of 2 and 1, the metabolite (2) was slightly less potent than disopyramide (1).