3-chloro-4-<2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)morpholin-4-yl>-1,2,5-thiadiazole | 75014-29-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-chloro-4-<2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)morpholin-4-yl>-1,2,5-thiadiazole
• CAS: 75014-29-8
• 化学式: C₁₁H₁₆ClN₃O₃S
• 分子量: 305.785
• InChiKey: IUEFIOYCWYRVSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  56.71
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-chloro-4-<2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)morpholin-4-yl>-1,2,5-thiadiazole 在 盐酸 、 potassium tert-butylate 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 6.17h， 生成 1-<(1,1-dimethylethyl)amino>-3-<<3-(2-hydroxymorpholin-4-yl)-1,2,5-thiadiazol-4-yl>oxy>-2-propanol
  参考文献：
  名称：

  Urinary metabolites of timolol from humans and laboratory animals. Syntheses and .beta.-adrenergic blocking activities

  摘要：

  Syntheses are reported for three metabolites (2-4) of timolol (1) formed by oxidative metabolism of the morpholine ring. GLC-MS comparisons are presented which establish that the two metabolites whose structures were previously in question are identical with their synthetic counterparts 2 and 3. In 2, metabolic oxidation of the 4-morpholinyl group of 1 had occurred at the carbon next to oxygen to give the 2-hydroxy-4-morpholinyl moiety, whereas in 3, the morpholine of 1 has been oxidized one step further and then ring opened to produce the N-(2-hydroxyethyl)glycine substituent. Biological testing of synthetic samples of the three major metabolites from human urine (3, 4, and 6) indicated that only 4, in which the morpholine moiety has been degraded to a 2-hydroxyethylamino group, had significant beta-adrenergic blocking activity (one-seventh that of timolol in anesthetized dogs).

  DOI：

  10.1021/jm00185a006
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 、 3-chloro-4-(2-hydroxymorpholin-4-yl)-1,2,5-thiadiazole 在 对甲苯磺酸 作用下， 以 氯仿 为溶剂， 反应 1.0h， 生成 3-chloro-4-<2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)morpholin-4-yl>-1,2,5-thiadiazole
  参考文献：
  名称：

  Urinary metabolites of timolol from humans and laboratory animals. Syntheses and .beta.-adrenergic blocking activities

  摘要：

  Syntheses are reported for three metabolites (2-4) of timolol (1) formed by oxidative metabolism of the morpholine ring. GLC-MS comparisons are presented which establish that the two metabolites whose structures were previously in question are identical with their synthetic counterparts 2 and 3. In 2, metabolic oxidation of the 4-morpholinyl group of 1 had occurred at the carbon next to oxygen to give the 2-hydroxy-4-morpholinyl moiety, whereas in 3, the morpholine of 1 has been oxidized one step further and then ring opened to produce the N-(2-hydroxyethyl)glycine substituent. Biological testing of synthetic samples of the three major metabolites from human urine (3, 4, and 6) indicated that only 4, in which the morpholine moiety has been degraded to a 2-hydroxyethylamino group, had significant beta-adrenergic blocking activity (one-seventh that of timolol in anesthetized dogs).

  DOI：

  10.1021/jm00185a006