4-(4-(difluoromethoxy)phenyl)-4-(3-(3-fluoropropoxy)phenyl)thiazolidine-2,5-dithione | 1361409-42-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 4-(4-(difluoromethoxy)phenyl)-4-(3-(3-fluoropropoxy)phenyl)thiazolidine-2,5-dithione
• CAS: 1361409-42-8
• 化学式: C₁₉H₁₆F₃NO₂S₃
• 分子量: 443.535
• InChiKey: XJWXESOPAQMPJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  30.49
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-(4-(difluoromethoxy)phenyl)-4-(3-(3-fluoropropoxy)phenyl)thiazolidine-2,5-dithione 在 叔丁基过氧化氢 、 ammonium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 12.0h， 生成 8-[4-(Difluoromethoxy)phenyl]-3,3-difluoro-8-[3-(3-fluoropropoxy)phenyl]-2,4-dihydroimidazo[1,5-a]pyrimidin-6-amine
  参考文献：
  名称：

  Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy

  摘要：

  The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5 h after oral co-administration of 300 mu mol/kg (R)-25 and efflux inhibitor GF120918 the brain A beta 40 level was reduced by 17% and the plasma A beta 40 level by 76%. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.079
• 作为产物：
  描述：

  3-(3-fluoropropoxy)benzaldehyde 在 盐酸 、 titanium(IV) tetraethanolate 、 正丁基锂 、 potassium tert-butylate 、 异丙基溴化镁 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 4-(4-(difluoromethoxy)phenyl)-4-(3-(3-fluoropropoxy)phenyl)thiazolidine-2,5-dithione
  参考文献：
  名称：

  Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy

  摘要：

  The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5 h after oral co-administration of 300 mu mol/kg (R)-25 and efflux inhibitor GF120918 the brain A beta 40 level was reduced by 17% and the plasma A beta 40 level by 76%. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.079