N-[1-(1S)-(3,5-difluoro-phenoxymethyl)-2-(2S)-hydroxy-4-(4R)-methoxy-5-(4-methoxy-benzyloxy)-pentyl]-2-[methyl-(2-(2S)-methyl-cyclopropyl-(S)-methyl)-amino]-6-[methyl-(propane-2-sulfonyl)-amino]-isonicotinamide | 1216935-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-[1-(1S)-(3,5-difluoro-phenoxymethyl)-2-(2S)-hydroxy-4-(4R)-methoxy-5-(4-methoxy-benzyloxy)-pentyl]-2-[methyl-(2-(2S)-methyl-cyclopropyl-(S)-methyl)-amino]-6-[methyl-(propane-2-sulfonyl)-amino]-isonicotinamide
• 英文别名: N-[(2S,3S,5R)-1-(3,5-difluorophenoxy)-3-hydroxy-5-methoxy-6-[(4-methoxyphenyl)methoxy]hexan-2-yl]-2-[methyl-[[(1S,2S)-2-methylcyclopropyl]methyl]amino]-6-[methyl(propan-2-ylsulfonyl)amino]pyridine-4-carboxamide
• CAS: 1216935-08-8
• 化学式: C₃₇H₅₀F₂N₄O₈S
• 分子量: 748.889
• InChiKey: KCEJCTFASYNQQT-CDKTVRDVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  52
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2-[(isopropylsulfonyl)(methyl)amino]-6-(methyl{[(1S,2S)-2-methylcyclopropyl]methyl}amino)isonicotinic acid 、 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以66%的产率得到N-[1-(1S)-(3,5-difluoro-phenoxymethyl)-2-(2S)-hydroxy-4-(4R)-methoxy-5-(4-methoxy-benzyloxy)-pentyl]-2-[methyl-(2-(2S)-methyl-cyclopropyl-(S)-methyl)-amino]-6-[methyl-(propane-2-sulfonyl)-amino]-isonicotinamide
  参考文献：
  名称：

  P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

  摘要：

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.041

文献信息

• P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
  作者：Jenny Adrian Meredith、Catarina Björklund、Hans Adolfsson、Katarina Jansson、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.ejmech.2009.10.041

  日期：2010.2

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.