(3-chloropropyl)cyclohexyl(4-fluorophenyl)methoxysilane | 137933-38-1

• 分子结构分类: 有机化合物
• 英文名称: (3-chloropropyl)cyclohexyl(4-fluorophenyl)methoxysilane
• 英文别名: 3-chloropropyl-cyclohexyl-(4-fluorophenyl)-methoxysilane
• CAS: 137933-38-1
• 化学式: C₁₆H₂₄ClFOSi
• 分子量: 314.903
• InChiKey: ZJOWLBDZXCRZAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (3-chloropropyl)cyclohexyl(4-fluorophenyl)methoxysilane 在 盐酸 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 32.0h， 生成 cyclohexyl(4-fluorophenyl)(3-hexamethyleniminopropyl)silanol
  参考文献：
  名称：

  Cyclohexy (4-fluorophenyl)(3-piperidinopropyl)silanol ((itp)-fluoro-hexahydro-sila-difenidol, p-F-HSSiD) and derivatives: synthesis and antimuscarinic properties

  摘要：

  Four different syntheses of the potent and selective muscarinic antagonist cyclohexyl(4-fluorophenyl)(3-piperidinopropyl)silanol (p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD (2b); isolated as hydrochloride 2b.HCl) are described (starting materials: (CH3O)3SiCH2CH2CH2Cl and Si(OCH3)4). In addition, the synthesis of the corresponding carbon analogue p-fluoro-hexahydro-difenidol (p-F-HHD (2a); isolated as 2a.HCl) and the syntheses of three p-F-HHSiD derivatives (3-5), with a modified cyclic amino group, are reported (3: piperidino/pyrrolidino exchange, isolated as 3.HCl; 4: piperidino/hexamethylenimino exchange, isolated as 4.HCl; 5: quaternization of 2b with methyl iodide). The chiral compounds 2a, 2b, 3, 4 and 5 were prepared as racemates. In functional pharmacological studies, 3-5 behaved as simple competitive antagonists at muscarinic M1 receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileal smooth muscle. The pyrrolidino (3) and hexamethylenimino (4) analogues of the parent drug p-F-HHSiD (2b) displayed the highest affinity for M1 and M3 receptors (pA2 values: 7.0-7.4) but exhibited lower affinity for cardiac M2 receptors (pA2: 5.9 and 6.0). Their affinity profile (M1 approximately M3 > M2) is different from that of p-F-HHSiD (2b) (M3 > M1 > M2), but qualitatively very similar to that of p-F-HHD (2a). The methiodide 5 exhibited the highest affinity for M1 receptors (pA2: 8.5) but lower affinity for M2 and M3 receptors by factors of 5.6 and 3.6, respectively.

  DOI：

  10.1016/0022-328x(91)80194-o
• 作为产物：
  描述：

  3-氯丙基-环己基-二甲氧基硅烷 、 对溴氟苯 在 正丁基锂 作用下， 生成 (3-chloropropyl)cyclohexyl(4-fluorophenyl)methoxysilane
  参考文献：
  名称：

  Cyclohexy (4-fluorophenyl)(3-piperidinopropyl)silanol ((itp)-fluoro-hexahydro-sila-difenidol, p-F-HSSiD) and derivatives: synthesis and antimuscarinic properties

  摘要：

  Four different syntheses of the potent and selective muscarinic antagonist cyclohexyl(4-fluorophenyl)(3-piperidinopropyl)silanol (p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD (2b); isolated as hydrochloride 2b.HCl) are described (starting materials: (CH3O)3SiCH2CH2CH2Cl and Si(OCH3)4). In addition, the synthesis of the corresponding carbon analogue p-fluoro-hexahydro-difenidol (p-F-HHD (2a); isolated as 2a.HCl) and the syntheses of three p-F-HHSiD derivatives (3-5), with a modified cyclic amino group, are reported (3: piperidino/pyrrolidino exchange, isolated as 3.HCl; 4: piperidino/hexamethylenimino exchange, isolated as 4.HCl; 5: quaternization of 2b with methyl iodide). The chiral compounds 2a, 2b, 3, 4 and 5 were prepared as racemates. In functional pharmacological studies, 3-5 behaved as simple competitive antagonists at muscarinic M1 receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileal smooth muscle. The pyrrolidino (3) and hexamethylenimino (4) analogues of the parent drug p-F-HHSiD (2b) displayed the highest affinity for M1 and M3 receptors (pA2 values: 7.0-7.4) but exhibited lower affinity for cardiac M2 receptors (pA2: 5.9 and 6.0). Their affinity profile (M1 approximately M3 > M2) is different from that of p-F-HHSiD (2b) (M3 > M1 > M2), but qualitatively very similar to that of p-F-HHD (2a). The methiodide 5 exhibited the highest affinity for M1 receptors (pA2: 8.5) but lower affinity for M2 and M3 receptors by factors of 5.6 and 3.6, respectively.

  DOI：

  10.1016/0022-328x(91)80194-o