(2e,5r)-5-Cyclopropyl-2-Imino-3-Methyl-5-{3-[5-(Prop-1-Yn-1-Yl)pyridin-3-Yl]phenyl}imidazolidin-4-One | 960075-74-5

• 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: (2e,5r)-5-Cyclopropyl-2-Imino-3-Methyl-5-{3-[5-(Prop-1-Yn-1-Yl)pyridin-3-Yl]phenyl}imidazolidin-4-One
• 英文别名: (5R)-2-amino-5-cyclopropyl-3-methyl-5-[3-(5-prop-1-ynylpyridin-3-yl)phenyl]imidazol-4-one
• CAS: 960075-74-5
• 化学式: C₂₁H₂₀N₄O
• 分子量: 344.416
• InChiKey: HORHMTMHXZJNQJ-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-溴-5-(1-丙炔)吡啶 在 正丁基锂 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 硼酸三异丙酯 、 碳酸氢铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 甲苯 为溶剂， 生成 (2e,5r)-5-Cyclopropyl-2-Imino-3-Methyl-5-{3-[5-(Prop-1-Yn-1-Yl)pyridin-3-Yl]phenyl}imidazolidin-4-One
  参考文献：
  名称：

  Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor

  摘要：

  From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Ab following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.013

文献信息

• ASPARTYL PROTEASE INHIBITORS
  申请人：Wu Yusheng

  公开号：US20070287692A1

  公开（公告）日：2007-12-13

  Disclosed are compounds of formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, U, W, X, R 1 , R 2 , R 6 , R 7 , R 30 and R 31 are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m 1 agonist or m 2 antagonist.

  本文披露了化合物I的结构，或其立体异构体、互变异构体、或其药用可接受的盐或溶剂，其中U、W、X、R1、R2、R6、R7、R30和R31如规范中所述。此外，还披露了抑制天冬氨酸蛋白酶的方法，特别是治疗心血管疾病、认知和神经退行性疾病的方法。还披露了使用化合物I的方法治疗认知或神经退行性疾病，其中与胆碱酯酶抑制剂或肌胆碱m1激动剂或m2拮抗剂结合使用。
• US8168641B2
  申请人：——

  公开号：US8168641B2

  公开（公告）日：2012-05-01
• US8629155B2
  申请人：——

  公开号：US8629155B2

  公开（公告）日：2014-01-14
• Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor
  作者：Jared N. Cumming、Elizabeth M. Smith、Lingyan Wang、Jeffrey Misiaszek、James Durkin、Jianping Pan、Ulrich Iserloh、Yusheng Wu、Zhaoning Zhu、Corey Strickland、Johannes Voigt、Xia Chen、Matthew E. Kennedy、Reshma Kuvelkar、Lynn A. Hyde、Kathleen Cox、Leonard Favreau、Michael F. Czarniecki、William J. Greenlee、Brian A. McKittrick、Eric M. Parker、Andrew W. Stamford

  DOI：10.1016/j.bmcl.2012.02.013

  日期：2012.4

  From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Ab following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound. (C) 2012 Elsevier Ltd. All rights reserved.