N-[4-((R)-2-Fluoromethyl-pyrrolidin-1-yl)-but-2-ynyl]-N-methyl-acetamide | 132377-39-0

• 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-((R)-2-Fluoromethyl-pyrrolidin-1-yl)-but-2-ynyl]-N-methyl-acetamide
• 英文别名: N-[4-[(2R)-2-(fluoromethyl)pyrrolidin-1-yl]but-2-ynyl]-N-methylacetamide
• CAS: 132377-39-0
• 化学式: C₁₂H₁₉FN₂O
• 分子量: 226.294
• InChiKey: ZTQOQOORKLHVHC-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 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：
  3

反应信息

• 作为产物：
  描述：

  N-甲基-N-(2-丙炔)乙酰胺 在 二甲氨基三氟化硫 、 copper(l) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-[4-((R)-2-Fluoromethyl-pyrrolidin-1-yl)-but-2-ynyl]-N-methyl-acetamide
  参考文献：
  名称：

  Muscarinic receptor binding and activation of second messengers by substituted N-methyl-N-[4-(1-azacycloalkyl)-2-butynyl]acetamides

  摘要：

  A series of substituted azacycloalkyl analogues of the muscarinic agonist UH 5 (N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl]acetamide, 1a) were synthesized and evaluated pharmacologically. These compounds were developed as intermediates for further derivatization leading to functionalized congeners of 1a. The compounds were synthesized by using a Mannich-type condensation of N-acetyl-N-methylpropargylamine to various substituted saturated azaheterocycles. The compounds were screened at a single concentration in competitive binding assays in rat cerebral cortical membranes against either [H-3]N-methylscopolamine (at 100-mu-M) or [H-3]oxotremorine-M (at 1-mu-M) labels. Candidates were then selected for further evaluation of their effect on phosphoinositide (PI) turnover in membranes from A9L cells transfected with cDNA of either m1-muscarinic cholinergic receptors (m1AChRs) or m3AChRs. The analogues were also tested for the inhibition of adenylate cyclase in NG108-15 cells expressing m4AChRs. The azetidine analogue of 1a had a K(i) value of 12 nM for the inhibition of [H-3]oxotremorine-M binding in rat brain and had an agonist potency at m1-, m3-, and m4AChRs comparable to 1a. The substituted 5- and 6-member ring analogues generally had lower binding affinities and were less potent than 1a in stimulating PI turnover. Several compounds were moderately effective in inhibiting cyclic AMP production in NG108-15 cells.

  DOI：

  10.1021/jm00107a029

文献信息

• Muscarinic receptor binding and activation of second messengers by substituted N-methyl-N-[4-(1-azacycloalkyl)-2-butynyl]acetamides
  作者：Barton J. Bradbury、Jesse Baumgold、Robert Paek、Udai Kammula、Jeff Zimmet、Kenneth A. Jacobson

  DOI：10.1021/jm00107a029

  日期：1991.3

  A series of substituted azacycloalkyl analogues of the muscarinic agonist UH 5 (N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl]acetamide, 1a) were synthesized and evaluated pharmacologically. These compounds were developed as intermediates for further derivatization leading to functionalized congeners of 1a. The compounds were synthesized by using a Mannich-type condensation of N-acetyl-N-methylpropargylamine to various substituted saturated azaheterocycles. The compounds were screened at a single concentration in competitive binding assays in rat cerebral cortical membranes against either [H-3]N-methylscopolamine (at 100-mu-M) or [H-3]oxotremorine-M (at 1-mu-M) labels. Candidates were then selected for further evaluation of their effect on phosphoinositide (PI) turnover in membranes from A9L cells transfected with cDNA of either m1-muscarinic cholinergic receptors (m1AChRs) or m3AChRs. The analogues were also tested for the inhibition of adenylate cyclase in NG108-15 cells expressing m4AChRs. The azetidine analogue of 1a had a K(i) value of 12 nM for the inhibition of [H-3]oxotremorine-M binding in rat brain and had an agonist potency at m1-, m3-, and m4AChRs comparable to 1a. The substituted 5- and 6-member ring analogues generally had lower binding affinities and were less potent than 1a in stimulating PI turnover. Several compounds were moderately effective in inhibiting cyclic AMP production in NG108-15 cells.