(S)-5-(4-(sec-butoxy)-3-methylphenyl)-2-(5-(((tert-butyldimethylsilyl)oxy)methyl)-3-ethylthiophen-2-yl)thiazole | 1374354-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: (S)-5-(4-(sec-butoxy)-3-methylphenyl)-2-(5-(((tert-butyldimethylsilyl)oxy)methyl)-3-ethylthiophen-2-yl)thiazole
• CAS: 1374354-38-7
• 化学式: C₂₇H₃₉NO₂S₂Si
• 分子量: 501.83
• InChiKey: UIOLZHDQZOFDJS-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.11
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  31.35
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-5-(4-(sec-butoxy)-3-methylphenyl)-2-(5-(((tert-butyldimethylsilyl)oxy)methyl)-3-ethylthiophen-2-yl)thiazole 在 氯化亚砜 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067
• 作为产物：
  描述：

  5-(((tert-butyldimethylsilyl)oxy)methyl)-3-ethylthiophene-2-carboxylic acid 在 劳森试剂 、 吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 氯仿 、 甲苯 为溶剂， 生成 (S)-5-(4-(sec-butoxy)-3-methylphenyl)-2-(5-(((tert-butyldimethylsilyl)oxy)methyl)-3-ethylthiophen-2-yl)thiazole
  参考文献：
  名称：

  Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists

  摘要：

  We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.067