(2R,5R,3E)-2-{3-[N-(benzyloxycarbonyl)amino]propyl}-5-[N-(9-fluorenylmethoxycarbonyl)-amino]-6-(4-methoxyphenyl)-4-methylhex-3-enoic acid | 1333081-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2R,5R,3E)-2-{3-[N-(benzyloxycarbonyl)amino]propyl}-5-[N-(9-fluorenylmethoxycarbonyl)-amino]-6-(4-methoxyphenyl)-4-methylhex-3-enoic acid
• 英文别名: (E,2R,5R)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(4-methoxyphenyl)-4-methyl-2-[3-(phenylmethoxycarbonylamino)propyl]hex-3-enoic acid
• CAS: 1333081-31-4
• 化学式: C₄₀H₄₂N₂O₇
• 分子量: 662.783
• InChiKey: CEGIIKSAVHZHSF-KUHOTGKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  49
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-chlorotrityl resin 、 (2R,5R,3E)-2-{3-[N-(benzyloxycarbonyl)amino]propyl}-5-[N-(9-fluorenylmethoxycarbonyl)-amino]-6-(4-methoxyphenyl)-4-methylhex-3-enoic acid 、 Fmoc-3-(2-萘基)-L-丙氨酸 、 Fmoc-Pbf-L-精氨酸 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 H-D-Tyr(Me)-ψ[(E)-CMe=CH]-Orn(Cbz)-Arg(Pbf)-Nal-Gly-(2-Cl)-Trt-OH
  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：

  N-苄氧羰基-2-硝基苯磺酰胺 在 potassium carbonate 、 苯硫酚 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 7.0h， 生成 (2R,5R,3E)-2-{3-[N-(benzyloxycarbonyl)amino]propyl}-5-[N-(9-fluorenylmethoxycarbonyl)-amino]-6-(4-methoxyphenyl)-4-methylhex-3-enoic acid
  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.