tert-butyl (5S)-3-benzyl-5-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-[[3-[(2R)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-5-methylbenzoyl]amino]propyl]-4-oxoimidazolidine-1-carboxylate | 1042903-81-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (5S)-3-benzyl-5-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-[[3-[(2R)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-5-methylbenzoyl]amino]propyl]-4-oxoimidazolidine-1-carboxylate
• CAS: 1042903-81-0
• 化学式: C₃₉H₄₆F₂N₄O₇
• 分子量: 720.814
• InChiKey: JEXBHOFOPDSCJR-WNQXLSPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  52
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (5S)-3-benzyl-5-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-[[3-[(2R)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-5-methylbenzoyl]amino]propyl]-4-oxoimidazolidine-1-carboxylate 在 三氟乙酸 作用下， 生成 N-((1S,2S)-1-((S)-1-benzyl-5-oxoimidazolidin-4-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-methylbenzamide
  参考文献：
  名称：

  Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

  摘要：

  Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.

  DOI：

  10.1016/j.bmcl.2008.04.050
• 作为产物：
  描述：

  3-(2-甲氧基甲基-吡咯烷-1-羰基)-5-甲基-苯甲酸 、 tert-butyl (5S)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-3-benzyl-4-oxoimidazolidine-1-carboxylate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 生成 tert-butyl (5S)-3-benzyl-5-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-[[3-[(2R)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-5-methylbenzoyl]amino]propyl]-4-oxoimidazolidine-1-carboxylate
  参考文献：
  名称：

  Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

  摘要：

  Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.

  DOI：

  10.1016/j.bmcl.2008.04.050

文献信息

• CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT
  申请人：Cumming Jared N.

  公开号：US20100152138A1

  公开（公告）日：2010-06-17

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is R is —C(O)—N(R 27 )(R 28 ) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

  本发明揭示了式I的化合物，或其药学上可接受的盐或溶剂，其中R1是R是—C（O）—N（R27）（R28）或，其余变量如规范中所定义。本发明还揭示了包括式I化合物的药物组成物。本发明还揭示了治疗认知或神经退行性疾病，如阿尔茨海默病的方法。本发明还揭示了包括式I化合物的药物组成物和治疗认知或神经退行性疾病的方法，其中该组成物与β-分泌酶抑制剂（非式I的）、HMG-CoA还原酶抑制剂、γ-分泌酶抑制剂、非甾体抗炎药、N-甲基-D-天门冬氨酸受体拮抗剂、胆碱酯酶抑制剂或抗淀粉样蛋白抗体结合使用。
• Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors
  作者：J.N. Cumming、T.X. Le、S. Babu、C. Carroll、X. Chen、L. Favreau、P. Gaspari、T. Guo、D.W. Hobbs、Y. Huang、U. Iserloh、M.E. Kennedy、R. Kuvelkar、G. Li、J. Lowrie、N.A. McHugh、L. Ozgur、J. Pan、E.M. Parker、K. Saionz、A.W. Stamford、C. Strickland、D. Tadesse、J. Voigt、L. Wang、Y. Wu、L. Zhang、Q. Zhang

  DOI：10.1016/j.bmcl.2008.04.050

  日期：2008.6

  Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.