(S)-2-azido-N-((R)-1-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino)-1-oxo-3-(perfluorophenyl)propan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide | 1207604-20-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-azido-N-((R)-1-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino)-1-oxo-3-(perfluorophenyl)propan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide
• 英文别名: (S)-2-azido-N-((S)-1-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino)-1-oxo-3-(perfluorophenyl)propan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide；(2S)-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-(2,3,4,5,6-pentafluorophenyl)propan-2-yl]-3-phenylpropanamide
• CAS: 1207604-20-3
• 化学式: C₃₆H₃₇F₅N₆O₅
• 分子量: 728.719
• InChiKey: MEOWRBUGZDLJTB-YALZDEJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  52
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4,4-difluoro-8-(hept-6-yne)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene 、 (S)-2-azido-N-((R)-1-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino)-1-oxo-3-(perfluorophenyl)propan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 甲苯 、 叔丁醇 为溶剂， 反应 2.5h， 以87%的产率得到(2S)-2-[[(2S)-2-[4-[4-(2,2-difluoro-4,6,10,12-tetramethyl-3-aza-1-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-1(12),4,6,8,10-pentaen-8-yl)butyl]triazol-1-yl]-3-phenylpropanoyl]amino]-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-(2,3,4,5,6-pentafluorophenyl)propan-2-yl]-3-phenylpropanamide
  参考文献：
  名称：

  Incorporation of Fluorinated Phenylalanine Generates Highly Specific Inhibitor of Proteasome’s Chymotrypsin-like Sites

  摘要：

  Proteasomal processing is conducted by three individual catalytic subunits, namely beta 1, beta 2, and beta 5. Subunit-specific inhibitors are useful tools In dissecting the role of these individual Subunits and are leads toward the development of antitumor agents. We here report that the presence of fluorinated phenyl-alanine derivatives in peptide based proteasome inhibitors has a profound effect on inhibitor potency and selectivity, Specifically, compound 4a emerges as one of the most beta 5 specific inhibitors known to date.

  DOI：

  10.1021/jm9015685
• 作为产物：
  描述：

  、 (S)-2-氨基-4-甲基-1-((R)-2-甲基环氧乙烷-2-基)-1-戊酮三氟乙酸盐 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以234 mg的产率得到(S)-2-azido-N-((R)-1-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino)-1-oxo-3-(perfluorophenyl)propan-2-ylamino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide
  参考文献：
  名称：

  Incorporation of Fluorinated Phenylalanine Generates Highly Specific Inhibitor of Proteasome’s Chymotrypsin-like Sites

  摘要：

  Proteasomal processing is conducted by three individual catalytic subunits, namely beta 1, beta 2, and beta 5. Subunit-specific inhibitors are useful tools In dissecting the role of these individual Subunits and are leads toward the development of antitumor agents. We here report that the presence of fluorinated phenyl-alanine derivatives in peptide based proteasome inhibitors has a profound effect on inhibitor potency and selectivity, Specifically, compound 4a emerges as one of the most beta 5 specific inhibitors known to date.

  DOI：

  10.1021/jm9015685

文献信息

• Inhibitors of the Trypsin-Like Site of the Proteasome and Methods of Use Thereof
  申请人：Kisselev Alexei

  公开号：US20120214732A1

  公开（公告）日：2012-08-23

  The present invention is an inhibitor of the trypsin-like β2/β2i sites of the proteasome. The inhibitor is characterized as being a peptide-based epoxyketone or vinyl sulfone that contains an arginine or 4-aminomethylene-L-phenylalanine at the C-terminus (i.e., at the P1 position). Methods for using the inhibitor to inhibit the activity of the β2/β2i site of a proteasome and treat a proteasome-mediated disease or condition are also described.

  本发明是一种蛋白酶体胰蛋白酶样β2/β2i位点的抑制剂。该抑制剂的特点是基于肽的环氧酮或乙烯砜，其C端（即P1位置）含有精氨酸或4-氨基亚甲基-L-苯丙氨酸。还描述了使用该抑制剂抑制蛋白酶体β2/β2i位点活性和治疗蛋白酶体介导的疾病或状况的方法。
• INHIBITORS OF THE TRYPSIN-LIKE SITE OF THE PROTEASOME AND METHODS OF USE THEREOF
  申请人：Trustees Of Dartmouth College

  公开号：US20130102527A1

  公开（公告）日：2013-04-25

  The present invention is an inhibitor of the trypsin-like β2/β2i sites of the proteasome. The inhibitor is characterized as being a peptide-based epoxyketone or vinyl sulfone that contains an arginine or 4-aminomethylene-L-phenylalanine at the C-terminus (i.e., at the P1 position). Methods for using the inhibitor to inhibit the activity of the β2/β2i site of a proteasome and treat a proteasome-mediated disease or condition are also described.

  本发明是一种蛋白酶体中类似胰蛋白酶的β2 / β2i位点的抑制剂。该抑制剂的特点是含有C-末端（即P1位置）的精氨酸或4-氨基甲基-L-苯丙氨酸的基于肽的环氧酮或乙烯基磺酰。还描述了使用该抑制剂来抑制蛋白酶体的β2 / β2i位点的活性和治疗蛋白酶体介导的疾病或病症的方法。
• US8455431B2
  申请人：——

  公开号：US8455431B2

  公开（公告）日：2013-06-04
• Incorporation of Fluorinated Phenylalanine Generates Highly Specific Inhibitor of Proteasome’s Chymotrypsin-like Sites
  作者：Paul P. Geurink、Nora Liu、Michiel P. Spaans、Sondra L. Downey、Adrianus M. C. H. van den Nieuwendijk、Gijsbert A. van der Marel、Alexei F. Kisselev、Bogdan I. Florea、Herman S. Overkleeft

  DOI：10.1021/jm9015685

  日期：2010.3.11

  Proteasomal processing is conducted by three individual catalytic subunits, namely beta 1, beta 2, and beta 5. Subunit-specific inhibitors are useful tools In dissecting the role of these individual Subunits and are leads toward the development of antitumor agents. We here report that the presence of fluorinated phenyl-alanine derivatives in peptide based proteasome inhibitors has a profound effect on inhibitor potency and selectivity, Specifically, compound 4a emerges as one of the most beta 5 specific inhibitors known to date.