(2R,5S)-3,3-Difluoro-5-iodomethyl-2-methyl-tetrahydro-furan | 187959-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢呋喃
• 英文名称: (2R,5S)-3,3-Difluoro-5-iodomethyl-2-methyl-tetrahydro-furan
• 英文别名: Odsiuxkhmarshw-uhnvwzdzsa-；(2R,5S)-3,3-difluoro-5-(iodomethyl)-2-methyloxolane
• CAS: 187959-68-8
• 化学式: C₆H₉F₂IO
• 分子量: 262.038
• InChiKey: ODSIUXKHMARSHW-UHNVWZDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,5S)-3,3-Difluoro-5-iodomethyl-2-methyl-tetrahydro-furan 以 甲醇 、 乙醚 为溶剂， 反应 4.0h， 生成 ((2S,5R)-4,4-Difluoro-5-methyl-tetrahydro-furan-2-ylmethyl)-trimethyl-ammonium; iodide
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Enantiomerically Pure Muscarinic Agonists:  Difluoromuscarines

  摘要：

  The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well. as ''unnatural'' ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M(2) (heart) and M(3) (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M(1) receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M(2) (heart force and rate) and M(3) (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces. significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M(2) and M(3) subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.

  DOI：

  10.1021/jm960742w
• 作为产物：
  描述：

  (2S,5R)-5-methyl-2-(iodomethyl)-4(2H)-dihydrofuranone 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2R,5S)-3,3-Difluoro-5-iodomethyl-2-methyl-tetrahydro-furan
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Enantiomerically Pure Muscarinic Agonists:  Difluoromuscarines

  摘要：

  The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well. as ''unnatural'' ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M(2) (heart) and M(3) (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M(1) receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M(2) (heart force and rate) and M(3) (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces. significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M(2) and M(3) subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.

  DOI：

  10.1021/jm960742w

表征谱图