β-secretase inhibitor IV

• 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: β-secretase inhibitor IV
• 英文别名: N¹-[(1S,2R)-3-(cyclopropylamino)-2-hydroxy-1-(phenylmethyl)propyl]-5-[methyl(methylsulfonyl)amino]-N³-[(1R)-1-phenylethyl]-1,3-benzenedicarboxamide；β-secrtase inhibitor IV；BACE-1 inhibitor IV；β-secretase (BACE1) inhibitor IV；Secretase inhibitor IV；inhibitor IV；N-[(1S,2R)-1-Benzyl-3-(cyclopropylamino)-2-hydroxypropyl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]isophthalamide；3-N-[(2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-1-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
• 化学式: C₃₁H₃₈N₄O₅S
• 分子量: 578.733
• InChiKey: VPNIQGRFZCTBEZ-SPTGULJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-苄基-2,3-环氧正丙基-氨基甲酸叔丁酯 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 19.5h， 生成 β-secretase inhibitor IV
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1)

  摘要：

  We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.

  DOI：

  10.1021/jm049379g

文献信息

• COMPOSITIONS FOR REDUCING BETA-AMYLOID-INDUCED NEUROTOXICITY COMPRISING BETA-SECRETASE INHIBITOR
  申请人：LEE Bong-Ho

  公开号：US20120122822A1

  公开（公告）日：2012-05-17

  Disclosed are a composition for reducing beta amyloid-induced neurotoxicity by inhibiting β-secretase activity, comprising a dibenzofuran derivative, and a method for preparing the same. Further disclosed is that the combination of the dibenzofuran derivative with a γ-secretase inhibitor or an anti-inflammatory agent shows higher activity with respect to reducing beta amyloid-induced neurotoxicity.

  本发明公开了一种通过抑制β-分泌酶活性减少β淀粉样蛋白诱导的神经毒性的组合物，包括二苯并呋喃衍生物，并公开了其制备方法。进一步公开了，将二苯并呋喃衍生物与γ-分泌酶抑制剂或抗炎药物结合使用，可显示出更高的减少β淀粉样蛋白诱导的神经毒性的活性。
• 2-AMINOPYRIMIDIN-4-ONE AND 2-AMINOPYRIDINE DERIVATIVES BOTH HAVING BACE1-INHIBITING ACTIVITY
  申请人：Yonezawa Shuji

  公开号：US20110237576A1

  公开（公告）日：2011-09-29

  The present invention provides a compound which has an effect of inhibiting amyloid-β production and is useful as a therapeutic agent for diseases induced by production, secretion and/or deposition of amyloid-β proteins. The present invention relates to a compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein A is optionally substituted carbocyclic diyl or optionally substituted heterocyclic diyl; B is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; R 1 is a group such as optionally substituted lower alkyl; R 2 is a group such as hydrogen; and R 3a and R 3b are each independently a group such as hydrogen, provided that the following compound is excluded.
• BACE1 INHIBITION FOR THE TREATMENT OF CANCER
  申请人：The Cleveland Clinic Foundation

  公开号：US20210069205A1

  公开（公告）日：2021-03-11

  Provided herein are compositions, systems, kits, and methods for treating a subject with cancer by administering a BACE1 inhibitor, such as MK-8931. In particular embodiments, the subject is treated with radiation (e.g., low dose radiation) first, and then administered a BACE1 inhibitor within a certain time window (e.g., about 3 hours to 6 days after the radiation treatment).
• [EN] 2-AMINOPYRIDIN-4-ONE AND 2-AMINOPYRIDINE DERIVATIVE BOTH HAVING BACE1-INHIBITING ACTIVITY<br/>[FR] 2-AMINOPYRIDIN-4-ONE ET DÉRIVÉ DE 2-AMINOPYRIDINE DONT L'ACTIVITÉ INHIBE LA BACE1
  申请人：SHIONOGI & CO

  公开号：WO2010047372A1

  公开（公告）日：2010-04-29

  アミロイドβ産生抑制作用を有し、アミロイドβタンパク質の産生、分泌および／または沈着により誘発される疾患の治療剤として有用な化合物を提供する。 式（Ｉ）： （式中、Ａは置換基を有していてもよい炭素環ジイルまたは置換基を有していてもよい複素環ジイルであり、Ｂは置換基を有していてもよい炭素環式基または置換基を有していてもよい複素環式基であり、Ｒ１は置換基を有していてもよい低級アルキル等であり、Ｒ２は水素等であり、Ｒ３ａおよびＲ３ｂは各々独立して水素等である。 ただし、以下の化合物を除く。） で示される化合物、もしくはその製薬上許容される塩またはそれらの溶媒和物。
• Structure-Based Design of Potent and Selective Cell-Permeable Inhibitors of Human β-Secretase (BACE-1)
  作者：Shawn J. Stachel、Craig A. Coburn、Thomas G. Steele、Kristen G. Jones、Elizabeth F. Loutzenhiser、Alison R. Gregro、Hemaka A. Rajapakse、Ming-Tain Lai、Ming-Chih Crouthamel、Min Xu、Katherine Tugusheva、Janet E. Lineberger、Beth L. Pietrak、Amy S. Espeseth、Xiao-Ping Shi、Elizabeth Chen-Dodson、M. Katharine Holloway、Sanjeev Munshi、Adam J. Simon、Lawrence Kuo、Joseph P. Vacca

  DOI：10.1021/jm049379g

  日期：2004.12.1

  We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.