NB-216 | 943924-04-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: NB-216
• 英文别名: (S)-4-{(R)-1-hydroxy-2-[1-(3-isopropyl-phenyl)-cyclopropylamino]-ethyl}-19-methoxymethyl-11-oxa-3,16-diaza-tricyclo[15.3.1.1*6,10*]docosa-1(21),6,8,10(22),17,19-hexaen-2-one；(4s)-4-[(1r)-1-Hydroxy-2-({1-[3-(1-Methylethyl)phenyl]cyclopropyl}amino)ethyl]-19-(Methoxymethyl)-11-Oxa-3,16-Diazatricyclo[15.3.1.1~6,10~]docosa-1(21),6(22),7,9,17,19-Hexaen-2-One；(4S)-4-[(1R)-1-hydroxy-2-[[1-(3-propan-2-ylphenyl)cyclopropyl]amino]ethyl]-19-(methoxymethyl)-11-oxa-3,16-diazatricyclo[15.3.1.16,10]docosa-1(21),6(22),7,9,17,19-hexaen-2-one
• CAS: 943924-04-7
• 化学式: C₃₅H₄₅N₃O₄
• 分子量: 571.76
• InChiKey: GCZHKZTYTMTFGU-JHOUSYSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  91.8
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 1% Pd/C 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 NB-216
  参考文献：
  名称：

  Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application

  摘要：

  A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Ab in human APP-wildtype transgenic (APP51/16) mice after oral administration. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.092

文献信息

• MACROCYCLIC COMPOUNDS USEFUL AS BASE INHIBITORS
  申请人：Betschart Claudia

  公开号：US20090029960A1

  公开（公告）日：2009-01-29

  The invention relates to novel macrocyclic compounds of the formula in which all of the variables are as defined in the specification, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.

  该发明涉及一种新型的大环化合物，其公式如下，在自由碱基形式或酸盐形式下，其中所有变量如规范中所定义，其制备方法，用作药物的方法以及包含它们的药物。
• US8039455B2
  申请人：——

  公开号：US8039455B2

  公开（公告）日：2011-10-18