2,2,2-Trifluoro-N-methyl-N-(1-methyl-prop-2-ynyl)-acetamide | 111903-31-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2,2,2-Trifluoro-N-methyl-N-(1-methyl-prop-2-ynyl)-acetamide
• 英文别名: N-but-3-yn-2-yl-2,2,2-trifluoro-N-methylacetamide
• CAS: 111903-31-2
• 化学式: C₇H₈F₃NO
• 分子量: 179.142
• InChiKey: YPRQKMNSGUHDFJ-UHFFFAOYSA-N

物化性质

• 沸点：
  50-51 °C(Press: 10 Torr)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  2,2,2-Trifluoro-N-methyl-N-(1-methyl-prop-2-ynyl)-acetamide 在 sodium hydroxide 、 sodium tetrahydroborate 、 溶剂黄146 、 copper(l) chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 49.5h， 生成 N-methyl-N-<4-(dimethylamino)-1-methyl-2-butynyl>-2-(3-chlorophenyl)acetamide
  参考文献：
  名称：

  Amide, urea, and carbamate analogs of the muscarinic agent [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride

  摘要：

  A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimulant activity and affinity of the new compounds we studied their ability to increase mean arterial blood pressure (MAP) in the pithed rat and their ability to displace the M1 receptor selective antagonist [H-3]pirenzepine from rabbit sympathetic ganglia. The quaternary ammonium derivatives of 1, but not their corresponding tertiary amines, displayed ganglionic stimulant properties. The urea derivative 14 and the acetamide derivative 18 were almost equipotent to 1 as ganglionic agonists. In addition, 14 and 18 showed only 2- to 3-fold less affinity to ganglionic muscarinic receptors than 1. Introduction of a methyl group in the 1 position of the butynyl chain of 1 and its 4-chlorophenyl analogue increased ganglionic stimulant potency. The resulting (+/-)-9 and (+/-)-11 were the most potent analogues in this study. They were found to be partial agonists and showed 5- and 16-fold higher potency than 1, respectively, in increasing the MAP. They also displayed 6- and 18-fold higher affinity than 1 for ganglionic M1 receptors. The (S)-enantiomers of 9 and 11 were 1.5- and 4.9-fold more potent, respectively, than their antipodes as ganglionic muscarinic stimulants. The C1-methyl-substituted urea and acetamide derivatives (15 and 19) were 1.5- and 3-fold less potent than 1 and displayed several-fold lower affinity for ganglionic M1 receptors. The new quaternary analogues retained the selectivity for ganglionic muscarinic receptors since they produced weak partial agonist effects on the guinea pig ileum and showed several-fold lower nicotinic activity than 1 in the frog rectus abdominis assay.

  DOI：

  10.1021/jm00093a011
• 作为产物：
  描述：

  N-(1-methyl-2-propynyl)trifluoroacetamide 、 碘甲烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以72%的产率得到2,2,2-Trifluoro-N-methyl-N-(1-methyl-prop-2-ynyl)-acetamide
  参考文献：
  名称：

  毒蕈碱剂N-甲基-N-（1-甲基-4-吡咯烷基-2-丁炔基）乙酰胺的衍生物。

  摘要：

  选择性部分毒蕈碱激动剂N-甲基-N-（1-甲基-4-吡咯烷基-2-丁炔基）乙酰胺（BM 5）的一系列叔和季类似物（无环酰亚胺，磺酰亚胺，N-乙酰磺酰胺和三氟乙酰胺） ，35）合成。发现化合物是分离的豚鼠回肠中的毒蕈碱激动剂，部分激动剂或拮抗剂。用甲磺酰基取代35的乙酰基或N-甲基及其类似物可消除功效，并降低对回肠毒蕈碱受体的亲和力。35的三氟乙酰胺类似物也比35具有更低的亲和力和效力。在与35有关的化合物中用乙酰基取代N-甲基会降低效力，但对亲和力没有明显影响。

  DOI：

  10.1021/jm00398a015

文献信息

• NILSSON, BJORN M.;RINGDAHL, BJORN;HACKSELL, ULI, J. MED. CHEM., 31,(1988) N 3, 577-582
  作者：NILSSON, BJORN M.、RINGDAHL, BJORN、HACKSELL, ULI

  DOI：——

  日期：——