[2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-(2-phenylpropan-2-ylcarbamoyl)pyridin-4-yl] methanesulfonate | 1022893-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-(2-phenylpropan-2-ylcarbamoyl)pyridin-4-yl] methanesulfonate
• CAS: 1022893-03-3
• 化学式: C₃₄H₃₄N₈O₇S
• 分子量: 698.759
• InChiKey: QZXYBEVSGDOCGA-WNJJXGMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  50
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  227
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-Methylsulfonyloxy-6-(2-phenylpropan-2-ylcarbamoyl)pyridine-2-carboxylic acid 、 (2S,3S)-3-amino-2-hydroxy-4-phenyl-N-[3-(2H-tetrazol-5-yl)phenyl]butanamide;hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-(2-phenylpropan-2-ylcarbamoyl)pyridin-4-yl] methanesulfonate
  参考文献：
  名称：

  Novel non-peptidic and small-sized BACE1 inhibitors

  摘要：

  Recently, we reported substrate-based beta-secretase (BACE1) inhibitors with a hydroxymethylcarbonyl (HMC) isostere as a substrate transition-state mimic. These inhibitors showed potent BACE1 inhibitory activities (similar to 1.2 nM IC50). In order to improve in vivo enzymatic stability and permeability across the blood-brain barrier, these penta-peptidic inhibitors would need to be further optimized. On the other hand, non-peptidic inhibitors possessing isophthalic residue at the P-2 position were reported from other research groups. We selected isophthalic-type aromatic residues at the P-2 position and an HMC isostere at the P-1 position as lead compounds. On the basis of the design approach focused on the conformer of docked inhibitor in BACE1, we found novel non-peptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P2 position. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.056

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
• Novel non-peptidic and small-sized BACE1 inhibitors
  作者：Yoshio Hamada、Hiroko Ohta、Naoko Miyamoto、Ryoji Yamaguchi、Abdellah Yamani、Koushi Hidaka、Tooru Kimura、Kazuki Saito、Yoshio Hayashi、Shoichi Ishiura、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2008.01.056

  日期：2008.3

  Recently, we reported substrate-based beta-secretase (BACE1) inhibitors with a hydroxymethylcarbonyl (HMC) isostere as a substrate transition-state mimic. These inhibitors showed potent BACE1 inhibitory activities (similar to 1.2 nM IC50). In order to improve in vivo enzymatic stability and permeability across the blood-brain barrier, these penta-peptidic inhibitors would need to be further optimized. On the other hand, non-peptidic inhibitors possessing isophthalic residue at the P-2 position were reported from other research groups. We selected isophthalic-type aromatic residues at the P-2 position and an HMC isostere at the P-1 position as lead compounds. On the basis of the design approach focused on the conformer of docked inhibitor in BACE1, we found novel non-peptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P2 position. (c) 2008 Elsevier Ltd. All rights reserved.