(3R,4S,5S)-3-amino-5-[(3-bromo-4-hydroxyphenyl)methyl]-1,1-dioxothian-4-ol | 947368-87-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3R,4S,5S)-3-amino-5-[(3-bromo-4-hydroxyphenyl)methyl]-1,1-dioxothian-4-ol
• CAS: 947368-87-8
• 化学式: C₁₂H₁₆BrNO₄S
• 分子量: 350.233
• InChiKey: CSNNEONDATWXHU-QRTLGDNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4S,5S)-3-amino-5-[(3-bromo-4-hydroxyphenyl)methyl]-1,1-dioxothian-4-ol 、 3-异丙基苯甲醛 在 sodium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (3S,4S,5R)-3-[(3-bromo-4-hydroxyphenyl)methyl]-1,1-dioxo-5-[(3-propan-2-ylphenyl)methylamino]thian-4-ol
  参考文献：
  名称：

  Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors

  摘要：

  This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray co-crystal structure. Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.038
• 作为产物：
  描述：

  tert-butyl (3aS,7R,7aR)-7-[(3-bromo-4-methoxyphenyl)methyl]-2,2-dimethyl-5,5-dioxo-4,6,7,7a-tetrahydro-3aH-thiopyrano[3,4-d][1,3]oxazole-3-carboxylate 在 盐酸 、 水 、 三溴化硼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 、 甲基叔丁基醚 为溶剂， 生成 (3R,4S,5S)-3-amino-5-[(3-bromo-4-hydroxyphenyl)methyl]-1,1-dioxothian-4-ol
  参考文献：
  名称：

  Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors

  摘要：

  This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray co-crystal structure. Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.038

文献信息

• Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors
  作者：Heinrich Rueeger、Jean-Michel Rondeau、Clive McCarthy、Henrik Möbitz、Marina Tintelnot-Blomley、Ulf Neumann、Sandrine Desrayaud

  DOI：10.1016/j.bmcl.2011.02.038

  日期：2011.4

  This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray co-crystal structure. Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described. (C) 2011 Elsevier Ltd. All rights reserved.