N-<4-(ethylmethylamino)-2-butynyl>-5-methyl-2-pyrrolidone | 112483-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: N-<4-(ethylmethylamino)-2-butynyl>-5-methyl-2-pyrrolidone
• 英文别名: N-[4-(ethylmethylamino)-2-butynyl]-5-methyl-2-pyrrolidone；1-[4-[Ethyl(methyl)amino]but-2-ynyl]-5-methylpyrrolidin-2-one
• CAS: 112483-23-5
• 化学式: C₁₂H₂₀N₂O
• 分子量: 208.304
• InChiKey: DHTBHIFUXKMUGU-UHFFFAOYSA-N

物化性质

• 沸点：
  118 °C(Press: 0.04 Torr)
• 密度：
  1.006±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-<4-(ethylmethylamino)-2-butynyl>-5-methyl-2-pyrrolidone 、 碘甲烷 以 丙酮 为溶剂， 生成 N-<4-(ethylmethylamino)-2-butynyl>-5-methyl-2-pyrrolidone methiodide
  参考文献：
  名称：

  5-Methyl-2-pyrrolidone analogs of oxotremorine as selective muscarinic agonists

  摘要：

  A series of N-(4-amino-2-butynyl)-5-methyl-2-pyrrolidones modified only in the amino group was synthesized. The compounds were agonists, partial agonists, and antagonists on the isolated guinea pig ileum. They had greater affinity and lower intrinsic efficacy at ileal muscarinic receptors than the identically modified N-(4-amino-2-butynyl)-2-pyrrolidones and N-(4-amino-2-butynyl)succinimides. Dissociation constants in the three series were correlated, suggesting that the compounds had similar mode of binding to muscarinic receptors. The 5-methyl-2-pyrrolidones were 10- to 20-fold less potent as muscarinic agonists on the guinea pig urinary bladder than on the ileum and also elicited lower relative maximal responses on the bladder. For example, the trimethylammonium (9) and azetidino (10) analogues were equipotent (EC50 = 0.2 microM) with the selective muscarinic stimulant N-(1-methyl-4-pyrrolidino-2-butynyl)-N-methylacetamide, BM 5 (2), as agonists on the ileum, but on the bladder 9 and 10 were relatively weak partial agonists, whereas 2 was an antagonist. Compound 10, like 2 and the dimethylamino analogue 8, also differentiated between centrally mediated muscarinic effects in vivo as it was potent in producing analgesia and hypothermia but did not elicit tremor. Instead, 10 antagonized oxotremorine-induced tremor. Thus, 10 resembled 2 in its actions except that the greater intrinsic efficacy of 10 shifted the balance between agonist and antagonist properties slightly toward agonism. Manipulation of intrinsic efficacy by minor changes in chemical structure is emphasized as a means of attaining selectivity.

  DOI：

  10.1021/jm00398a031
• 作为产物：
  描述：

  聚合甲醛 、 5-甲基-N-(2-丙炔基)-2-吡咯烷酮 、 N-乙基甲基胺 在 copper(l) chloride 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以65%的产率得到N-<4-(ethylmethylamino)-2-butynyl>-5-methyl-2-pyrrolidone
  参考文献：
  名称：

  5-Methyl-2-pyrrolidone analogs of oxotremorine as selective muscarinic agonists

  摘要：

  A series of N-(4-amino-2-butynyl)-5-methyl-2-pyrrolidones modified only in the amino group was synthesized. The compounds were agonists, partial agonists, and antagonists on the isolated guinea pig ileum. They had greater affinity and lower intrinsic efficacy at ileal muscarinic receptors than the identically modified N-(4-amino-2-butynyl)-2-pyrrolidones and N-(4-amino-2-butynyl)succinimides. Dissociation constants in the three series were correlated, suggesting that the compounds had similar mode of binding to muscarinic receptors. The 5-methyl-2-pyrrolidones were 10- to 20-fold less potent as muscarinic agonists on the guinea pig urinary bladder than on the ileum and also elicited lower relative maximal responses on the bladder. For example, the trimethylammonium (9) and azetidino (10) analogues were equipotent (EC50 = 0.2 microM) with the selective muscarinic stimulant N-(1-methyl-4-pyrrolidino-2-butynyl)-N-methylacetamide, BM 5 (2), as agonists on the ileum, but on the bladder 9 and 10 were relatively weak partial agonists, whereas 2 was an antagonist. Compound 10, like 2 and the dimethylamino analogue 8, also differentiated between centrally mediated muscarinic effects in vivo as it was potent in producing analgesia and hypothermia but did not elicit tremor. Instead, 10 antagonized oxotremorine-induced tremor. Thus, 10 resembled 2 in its actions except that the greater intrinsic efficacy of 10 shifted the balance between agonist and antagonist properties slightly toward agonism. Manipulation of intrinsic efficacy by minor changes in chemical structure is emphasized as a means of attaining selectivity.

  DOI：

  10.1021/jm00398a031

文献信息

• RINGDAHL, BJORN, J. MED. CHEM., 31,(1988) N 3, 683-688
  作者：RINGDAHL, BJORN

  DOI：——

  日期：——
• 5-Methyl-2-pyrrolidone analogs of oxotremorine as selective muscarinic agonists
  作者：Bjoern Ringdahl

  DOI：10.1021/jm00398a031

  日期：1988.3

  A series of N-(4-amino-2-butynyl)-5-methyl-2-pyrrolidones modified only in the amino group was synthesized. The compounds were agonists, partial agonists, and antagonists on the isolated guinea pig ileum. They had greater affinity and lower intrinsic efficacy at ileal muscarinic receptors than the identically modified N-(4-amino-2-butynyl)-2-pyrrolidones and N-(4-amino-2-butynyl)succinimides. Dissociation constants in the three series were correlated, suggesting that the compounds had similar mode of binding to muscarinic receptors. The 5-methyl-2-pyrrolidones were 10- to 20-fold less potent as muscarinic agonists on the guinea pig urinary bladder than on the ileum and also elicited lower relative maximal responses on the bladder. For example, the trimethylammonium (9) and azetidino (10) analogues were equipotent (EC50 = 0.2 microM) with the selective muscarinic stimulant N-(1-methyl-4-pyrrolidino-2-butynyl)-N-methylacetamide, BM 5 (2), as agonists on the ileum, but on the bladder 9 and 10 were relatively weak partial agonists, whereas 2 was an antagonist. Compound 10, like 2 and the dimethylamino analogue 8, also differentiated between centrally mediated muscarinic effects in vivo as it was potent in producing analgesia and hypothermia but did not elicit tremor. Instead, 10 antagonized oxotremorine-induced tremor. Thus, 10 resembled 2 in its actions except that the greater intrinsic efficacy of 10 shifted the balance between agonist and antagonist properties slightly toward agonism. Manipulation of intrinsic efficacy by minor changes in chemical structure is emphasized as a means of attaining selectivity.