5-甲基-N-(2-丙炔基)-2-吡咯烷酮 | 18327-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 5-甲基-N-(2-丙炔基)-2-吡咯烷酮
• 英文名称: 5-methyl-N-(2-propynyl)-2-pyrrolidone
• 英文别名: 5-methyl-N-2-propynyl-2-pyrrolidone；5-methyl-1-prop-2-ynyl-pyrrolidin-2-one；1-(2-Propinyl)-5-methyl-2-pyrrolidinon；N-Propargyl-5-methyl-2-pyrrolidon；5-Methyl-1-prop-2-ynylpyrrolidin-2-one
• CAS: 18327-34-9
• 化学式: C₈H₁₁NO
• 分子量: 137.181
• InChiKey: AXTFWTYUCLLLEO-UHFFFAOYSA-N

物化性质

• 沸点：
  75 °C(Press: 1.0 Torr)
• 密度：
  1.022±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-甲基-N-(2-丙炔基)-2-吡咯烷酮 在 溴化氰 、 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 、 乙醚 为溶剂， 反应 20.0h， 生成 N-<4-(dimethylamino)-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
• 作为产物：
  描述：

  5-甲基-2-吡咯烷酮 、 3-溴丙炔 在 氢氧化钾 、 四丁基溴化铵 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以87%的产率得到5-甲基-N-(2-丙炔基)-2-吡咯烷酮
  参考文献：
  名称：

  .beta.-Lactam analogs of oxotremorine. 3- and 4-Methyl-substituted 2-azetidinones

  摘要：

  Four beta-lactam analogues (8-11) of oxotremorine were synthesized and assayed for muscarinic and antimuscarinic activity on the isolated guinea pig ileum. The pharmacological results were compared with those obtained previously with the beta-lactam analogue 7 and the 3-, 4-, and 5-methyl-substituted 2-pyrrolidones 2-6. The new compounds were less potent than the corresponding 2-pyrrolidones, regardless of whether they showed agonist (10 and 11), partial agonist (8), or antagonist properties (9) in the ileum assay. The agonists 10 and 11 were about 200-fold less potent than 7. Compounds 8-11 also were less potent than the similarly substituted 2-pyrrolidones in inhibiting the binding of the muscarinic antagonist (-)-[3H]-N-methylscopolamine in homogenates of the rat cerebral cortex.

  DOI：

  10.1021/jm00164a018

文献信息

• Cholinergic activity of acetylenic imidazoles and related compounds
  作者：Malcolm W. Moon、Connie G. Chidester、Richard F. Heier、Jeanette K. Morris、R. James Collins、Roland R. Russell、Jonathan W. Francis、G. Patrick Sage、Vimala H. Sethy

  DOI：10.1021/jm00112a002

  日期：1991.8

  alpha-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine

  制备了一系列与oxotremorine相关的炔属咪唑（1a），并通过体外结合试验和小鼠体内药理学试验评估了它们为胆碱能药物。1- [4-（1H-咪唑-1-基）-2-丁炔基] -2-吡咯烷酮（1b）是胆碱能激动剂，氧代雷莫林的效力为二分之一。在咪唑环中具有5-或2-甲基取代基的1b的类似物（化合物1c和1g）是胆碱能部分激动剂。1b在吡咯烷酮环的5位（7b）或炔链的α位（8b）具有甲基取代基的类似物是拮抗剂。制备了这些咪唑乙炔的各种类似物，其中吡咯烷酮环被酰胺，氨基甲酸酯或尿素残基取代。含有5-甲基咪唑作为胺取代基的几种化合物是部分激动剂。将咪唑化合物的活性与相关的吡咯烷和二甲胺类似物的活性进行比较。提出了这些化合物在毒蕈碱受体上的激动剂和拮抗剂构象。
• Tertiary 3- and 4-haloalkylamine analogs of oxotremorine as prodrugs of potent muscarinic agonists
  作者：Bjorn Ringdahl、Margareth Roch、Donald J. Jenden

  DOI：10.1021/jm00396a024

  日期：1988.1

  A series of tertiary 3- and 4-haloalkylamines related to the muscarinic agent oxotremorine was synthesized. The compounds cyclized in neutral aqueous solution to quaternary ammonium salts, which, in contrast to the parent haloalkylamines, were potent muscarinic agonists in vitro. When administered systemically to mice, the haloalkylamines produced central (tremor and analgesia) and peripheral (salivation)

  合成了一系列与毒蕈碱剂oxotremorine有关的3-和4-卤代烷基叔胺。该化合物在中性水溶液中环化成季铵盐，与母体卤代烷基胺相反，季铵盐在体外是有效的毒蕈碱激动剂。当全身性给予小鼠时，卤代烷基胺产生中枢（震颤和镇痛）和外周（唾液化）毒蕈碱作用。中央效能取决于环化速率和给药途径。N-甲基-N-（4-氯丁基）胺衍生物7快速环化（t1 / 2在37°C下不到0.4分钟）并在iv注射但在ip注射时没有震颤，而N-甲基-N-（ 3-氯丙基）胺3缓慢环化（t1 / 2 = 436分钟），并且通过任一给药途径均无震颤。N-甲基-N-（3-溴丙基）胺4（t1 / 2 = 11分钟）及其碘代类似物5（t1 / 2 = 14分钟）在诱发静脉内和腹膜内注射毒蕈碱效果方面非常有效。老鼠。结论是，氧代苯丁胺的卤代烷基胺类似物可以在体内用作强季铵盐的前药，并且它们能够绕过血盐对这类盐的血脑屏障。
• Alkylating partial muscarinic agonists related to oxotremorine. N-[4-[(2-Haloethyl)methylamino]-2-butynyl]-5-methyl-2-pyrrolidones
  作者：Bjorn Ringdahl、Margareth Roch、Esther D. Katz、Maria C. Frankland

  DOI：10.1021/jm00123a027

  日期：1989.3

  N-[4-[(2-Chloroethyl)methylamino]-2-butynyl]-5-methyl-2-pyrrolidone (3) and N-[4-[(2-bromoethyl)methylamino]-2-butynyl]-5-methyl-2- pyrrolidone (4) were synthesized. Compounds 3 and 4 cyclized in neutral aqueous solution to an aziridinium ion (4A). The rate constants for the cyclization of 3 and 4 at 37 degrees C were 0.025 and 0.89 min-1, respectively. The aziridinium ion was equipotent with carbachol

  N- [4-[（2-氯乙基）甲基氨基] -2-丁炔基] -5-甲基-2-吡咯烷酮（3）和N- [4-[（2-溴乙基）甲基氨基] -2-丁炔基] -5合成了-甲基-2-吡咯烷酮（4）。化合物3和4在中性水溶液中环化成叠氮鎓离子（4A）。3和4在37摄氏度环化的速率常数分别为0.025和0.89 min-1。在分离的豚鼠回肠上，叠氮鎓离子与卡巴胆碱作为毒蕈碱激动剂是等价的。在使大鼠大脑皮层匀浆中的毒蕈碱受体烷基化方面，它比相应的2-吡咯烷酮衍生物（2A）更有效。这种较高的效力是由于与2A相比，4A的受体亲和力更大，而不是毒蕈碱受体的烷基化速率常数更大。
• RINGDAHL, B.;ROCH, M.;KATZ, E. D.;FRANKLAND, M. C., J. MED. CHEM., 32,(1989) N, C. 659-663
  作者：RINGDAHL, B.、ROCH, M.、KATZ, E. D.、FRANKLAND, M. C.

  DOI：——

  日期：——
• RINGDAHL, BJORN;ROCH, MARGARETH;JENDEN, DONALD J., J. MED. CHEM., 31,(1988) N 1, 160-164
  作者：RINGDAHL, BJORN、ROCH, MARGARETH、JENDEN, DONALD J.

  DOI：——

  日期：——