tert-butyl (E)-3-[(4R,5R)-N-(tert-butoxycarbonyl)-4-(4-methoxybenzyl)-5-methyl-1,3-oxazolidin-2-on-5-yl]but-2-enoate | 1361407-66-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: tert-butyl (E)-3-[(4R,5R)-N-(tert-butoxycarbonyl)-4-(4-methoxybenzyl)-5-methyl-1,3-oxazolidin-2-on-5-yl]but-2-enoate
• 英文别名: tert-butyl (4R,5R)-4-[(4-methoxyphenyl)methyl]-5-methyl-5-[(E)-4-[(2-methylpropan-2-yl)oxy]-4-oxobut-2-en-2-yl]-2-oxo-1,3-oxazolidine-3-carboxylate
• CAS: 1361407-66-0
• 化学式: C₂₅H₃₅NO₇
• 分子量: 461.555
• InChiKey: HVPGMIFEFNMLFL-MCGNTTHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (E)-3-[(4R,5R)-N-(tert-butoxycarbonyl)-4-(4-methoxybenzyl)-5-methyl-1,3-oxazolidin-2-on-5-yl]but-2-enoate 在 六氟合硅酸 、 水 、 copper(l) cyanide 、 potassium carbonate 、 苯硫酚 、 三苯基膦 、 lithium chloride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 正戊烷 为溶剂， 反应 18.0h， 生成 tert-butyl (2R,5R,3E)-2-{3-[N-(benzyloxycarbonyl)amino]propyl}-5-[N-(tert-butoxycarbonyl)-amino]-6-(4-methoxyphenyl)-3,4-dimethylhex-3-enoate
  参考文献：
  名称：

  Structure–Activity Relationship Study of a CXC Chemokine Receptor Type 4 Antagonist, FC131, Using a Series of Alkene Dipeptide Isosteres

  摘要：

  A structure-activity relationship study on a highly potent CXC chemokine receptor type 4 (CXCR4) antagonist, FC131 [cyclo(-D-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], was carried out using a series of alkene isosteres of the D-Tyr(1)-L/D-Arg(2) dipeptide to investigate the binding mode of FC131 and its derivatives with CXCR4. The structure-activity relationships of isostere-containing FC131 analogues were similar to those of the parent FC131 and its derivatives, suggesting that a trans-conformer of the D-Tyt(1)-Arg(2) peptide bond is the dominant contributor to the bioactive conformations of FC131. Although NMR analysis demonstrated that the two conformations of the peptidomimetic containing the D-Tyr(1)-D-Arg(2) isostere are possible, binding-mode prediction indicated that the orientations of the alkene motif within D-Tyr(1)-MeArg(2) peptidomimetics depend on the chirality of Arg(2) and the beta-methyl group of the isostere unit, which makes the dominant contribution for binding to the receptor. The most potent FC122 [cyclo(-D-Tyr(1)-D-MeArg(2)-Arg(3)-Nal(4)-Gly(5)-)] bound with CXCR4 by a binding mode different from that of FC131.

  DOI：

  10.1021/jm2016914
• 作为产物：
  描述：

  (R)-N-(tert-butoxycarbonyl)-2-amino-3-(p-methyloxyphenyl)-N-methoxy-N-methylpropionamide 在 cerium(III) chloride 、 二甲基硫 、 sodium hydride 、 臭氧 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 、 mineral oil 为溶剂， 反应 18.25h， 生成 tert-butyl (E)-3-[(4R,5R)-N-(tert-butoxycarbonyl)-4-(4-methoxybenzyl)-5-methyl-1,3-oxazolidin-2-on-5-yl]but-2-enoate
  参考文献：
  名称：

  Structure–Activity Relationship Study of a CXC Chemokine Receptor Type 4 Antagonist, FC131, Using a Series of Alkene Dipeptide Isosteres

  摘要：

  A structure-activity relationship study on a highly potent CXC chemokine receptor type 4 (CXCR4) antagonist, FC131 [cyclo(-D-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], was carried out using a series of alkene isosteres of the D-Tyr(1)-L/D-Arg(2) dipeptide to investigate the binding mode of FC131 and its derivatives with CXCR4. The structure-activity relationships of isostere-containing FC131 analogues were similar to those of the parent FC131 and its derivatives, suggesting that a trans-conformer of the D-Tyt(1)-Arg(2) peptide bond is the dominant contributor to the bioactive conformations of FC131. Although NMR analysis demonstrated that the two conformations of the peptidomimetic containing the D-Tyr(1)-D-Arg(2) isostere are possible, binding-mode prediction indicated that the orientations of the alkene motif within D-Tyr(1)-MeArg(2) peptidomimetics depend on the chirality of Arg(2) and the beta-methyl group of the isostere unit, which makes the dominant contribution for binding to the receptor. The most potent FC122 [cyclo(-D-Tyr(1)-D-MeArg(2)-Arg(3)-Nal(4)-Gly(5)-)] bound with CXCR4 by a binding mode different from that of FC131.

  DOI：

  10.1021/jm2016914

文献信息

• Structure–Activity Relationship Study of a CXC Chemokine Receptor Type 4 Antagonist, FC131, Using a Series of Alkene Dipeptide Isosteres
  作者：Kazuya Kobayashi、Shinya Oishi、Ryoko Hayashi、Kenji Tomita、Tatsuhiko Kubo、Noriko Tanahara、Hiroaki Ohno、Yasushi Yoshikawa、Toshio Furuya、Masaru Hoshino、Nobutaka Fujii

  DOI：10.1021/jm2016914

  日期：2012.3.22

  A structure-activity relationship study on a highly potent CXC chemokine receptor type 4 (CXCR4) antagonist, FC131 [cyclo(-D-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], was carried out using a series of alkene isosteres of the D-Tyr(1)-L/D-Arg(2) dipeptide to investigate the binding mode of FC131 and its derivatives with CXCR4. The structure-activity relationships of isostere-containing FC131 analogues were similar to those of the parent FC131 and its derivatives, suggesting that a trans-conformer of the D-Tyt(1)-Arg(2) peptide bond is the dominant contributor to the bioactive conformations of FC131. Although NMR analysis demonstrated that the two conformations of the peptidomimetic containing the D-Tyr(1)-D-Arg(2) isostere are possible, binding-mode prediction indicated that the orientations of the alkene motif within D-Tyr(1)-MeArg(2) peptidomimetics depend on the chirality of Arg(2) and the beta-methyl group of the isostere unit, which makes the dominant contribution for binding to the receptor. The most potent FC122 [cyclo(-D-Tyr(1)-D-MeArg(2)-Arg(3)-Nal(4)-Gly(5)-)] bound with CXCR4 by a binding mode different from that of FC131.