cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-D-Arg-L-Arg-L-Nal-Gly-] | 1333081-30-3

• 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: cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-D-Arg-L-Arg-L-Nal-Gly-]
• 英文别名: 2-[3-[(2S,5S,11R,12E,14S)-14-[3-(diaminomethylideneamino)propyl]-11-[(4-hydroxyphenyl)methyl]-12,13-dimethyl-5-(naphthalen-2-ylmethyl)-3,6,9,15-tetraoxo-1,4,7,10-tetrazacyclopentadec-12-en-2-yl]propyl]guanidine
• CAS: 1333081-30-3
• 化学式: C₃₉H₅₂N₁₀O₅
• 分子量: 740.906
• InChiKey: QRXBSCHWFCNZSX-MXRRXXMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  54
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  265
• 氢给体数：
  9
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-D-Arg-L-Arg-L-Nal-Gly-] 、 三氟乙酸 以 乙腈 为溶剂， 以9.51 mg的产率得到cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-D-Arg-L-Arg-L-Nal-Gly-]
  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：

  cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-Orn(Cbz)-Arg(Pbf)-Nal-Gly-] 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 cyclo[-D-Tyr(Me)-ψ[(E)-CMe=CMe]-D-Arg-L-Arg-L-Nal-Gly-]
  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.