6-N-[(1R)-1-(4-chlorophenyl)ethyl]-2-N-[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]-4-oxopyran-2,6-dicarboxamide | 1095513-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-N-[(1R)-1-(4-chlorophenyl)ethyl]-2-N-[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]-4-oxopyran-2,6-dicarboxamide
• CAS: 1095513-71-5
• 化学式: C₃₂H₂₈ClN₇O₆
• 分子量: 642.071
• InChiKey: ODUYIYLBCITWDI-BBSHIGFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  188
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2S,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 在 盐酸 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-N-[(1R)-1-(4-chlorophenyl)ethyl]-2-N-[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]-4-oxopyran-2,6-dicarboxamide
  参考文献：
  名称：

  Structure–activity relationship study of BACE1 inhibitors possessing a chelidonic or 2,6-pyridinedicarboxylic scaffold at the P2 position

  摘要：

  We have previously reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. While these inhibitors exhibited potent activities in enzymatic and cellular assays (KMI-429 in particular inhibited A beta production in vivo), these inhibitors contained some natural amino acids that seemed to be required to improve enzymatic stability in vivo and permeability across the blood-brain barrier, so as to be practical drug. Recently, we synthesized non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold at the P-2 position. Herein we report the SAR study of BACE1 inhibitors possessing this heterocyclic scaffold, a chelidonic or 2,6-pyridinedicarboxylic moiety. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.007

文献信息

• NOVEL COMPOUND HAVING BETA-SECRETASE INHIBITORY ACTIVITY
  申请人：Kiso Yoshiaki

  公开号：US20100137606A1

  公开（公告）日：2010-06-03

  A novel compound represented by the formula (1) below which has β-secretase inhibitory activity, its pharmaceutically acceptable salt or a prodrug thereof. wherein Ar is a substituted or unsubstituted 5 to 6 membered mono cyclic aromatic group; R 1 , R 2 and R 3 are hydrogen atom, substituted or unsubstituted alkyl group or the like, or R 2 and R 3 may be taken together with the adjacent nitrogen atom and carbon atom respectively to form a 3 to 6 membered ring; R 4 is C 1-6 alkyl group, C 1-6 alkyl group substituted by phenyl, phenylthio, or a hetero ring, or the like; A is represented by the formula below: wherein X and Y are oxygen atom, NH or sulfur atom, Z is hydrogen atom, hydroxy group which may be substituted, amino group, thiol group, or the like; and B is hydroxy group, substituted or unsubstituted amino group, substituted or unsubstituted aliphatic or aromatic amino group, or the like.
• US8344002B2
  申请人：——

  公开号：US8344002B2

  公开（公告）日：2013-01-01