(S)-2-[(3S,6S,11R,18R)-11-tert-Butoxycarbonylamino-3-butyl-6-(4-hydroxy-benzyl)-2,5,8,12,19-pentaoxo-1,4,7,13-tetraaza-cyclononadec-18-ylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester | 115295-05-1

• 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-[(3S,6S,11R,18R)-11-tert-Butoxycarbonylamino-3-butyl-6-(4-hydroxy-benzyl)-2,5,8,12,19-pentaoxo-1,4,7,13-tetraaza-cyclononadec-18-ylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester
• CAS: 115295-05-1
• 化学式: C₄₃H₅₉N₇O₁₀
• 分子量: 833.982
• InChiKey: MNAQJDRVKJTVLU-IXNRCNHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  60.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  246.15
• 氢给体数：
  8.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (S)-2-[(3S,6S,11R,18R)-11-tert-Butoxycarbonylamino-3-butyl-6-(4-hydroxy-benzyl)-2,5,8,12,19-pentaoxo-1,4,7,13-tetraaza-cyclononadec-18-ylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以81%的产率得到(S)-2-[(3S,6S,11R,18R)-11-tert-Butoxycarbonylamino-3-butyl-6-(4-hydroxy-benzyl)-2,5,8,12,19-pentaoxo-1,4,7,13-tetraaza-cyclononadec-18-ylamino]-3-(1H-indol-3-yl)-propionic acid
  参考文献：
  名称：

  Synthesis and binding affinities of cyclic and related linear analogs of CCK8 selective for central receptors

  摘要：

  To investigate the role of the sulfate group and the influence of cyclization on the biological properties of conformationally constrained CCK8 analogues, three series of compounds were synthesized: Boc-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (1), Boc-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (2), and Boc-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (3) (series A); Boc-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (4), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (5), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (6), and Boc-D-Glu-Tyr(SO3H)-Nle-D-Nle-Trp-Asp-Phe-NH2 (7) (series B); and Boc-gamma-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (8), Boc-gamma-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (9), and Boc-gamma-D-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (10) (series C). The selectivity of these peptides was studied by measuring their ability to displace [3H]propionyl-CCK8 from guinea pig brain and pancreatic membranes. All the peptides displayed low affinities (KI values around 10(-6) M) for the pancreatic receptors (A type). In contrast, both sulfated and nonsulfated cyclic analogues displayed high affinities for central-type binding sites (B type), especially compounds belonging to series C [KI(8) = 4.7 nM and KI(9) = 0.56 nM]. In all series the linear analogues had relatively poor affinities (KI approximately 300 nM) for B-type receptors. Compound 9 was the most potent (KI = 0.56 nM) and selective [KI(pancreas)/KI(brain) = 4464] for central-type CCK receptors of guinea pig. The cyclization of the N-terminal region of CCK8 permits one therefore to obtain probes for central receptors, and small changes directed toward the cyclic part modulate the affinity for these receptors.

  DOI：

  10.1021/jm00126a007
• 作为产物：
  描述：

  Boc-γ-D-Glu(α-OBzl)-Tyr-Nle-D-Lys(Z)-Trp-OCH3 在 palladium on activated charcoal 叠氮磷酸二苯酯 、 氢气 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.0h， 生成 (S)-2-[(3S,6S,11R,18R)-11-tert-Butoxycarbonylamino-3-butyl-6-(4-hydroxy-benzyl)-2,5,8,12,19-pentaoxo-1,4,7,13-tetraaza-cyclononadec-18-ylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester
  参考文献：
  名称：

  Synthesis and binding affinities of cyclic and related linear analogs of CCK8 selective for central receptors

  摘要：

  To investigate the role of the sulfate group and the influence of cyclization on the biological properties of conformationally constrained CCK8 analogues, three series of compounds were synthesized: Boc-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (1), Boc-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (2), and Boc-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (3) (series A); Boc-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (4), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (5), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (6), and Boc-D-Glu-Tyr(SO3H)-Nle-D-Nle-Trp-Asp-Phe-NH2 (7) (series B); and Boc-gamma-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (8), Boc-gamma-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (9), and Boc-gamma-D-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (10) (series C). The selectivity of these peptides was studied by measuring their ability to displace [3H]propionyl-CCK8 from guinea pig brain and pancreatic membranes. All the peptides displayed low affinities (KI values around 10(-6) M) for the pancreatic receptors (A type). In contrast, both sulfated and nonsulfated cyclic analogues displayed high affinities for central-type binding sites (B type), especially compounds belonging to series C [KI(8) = 4.7 nM and KI(9) = 0.56 nM]. In all series the linear analogues had relatively poor affinities (KI approximately 300 nM) for B-type receptors. Compound 9 was the most potent (KI = 0.56 nM) and selective [KI(pancreas)/KI(brain) = 4464] for central-type CCK receptors of guinea pig. The cyclization of the N-terminal region of CCK8 permits one therefore to obtain probes for central receptors, and small changes directed toward the cyclic part modulate the affinity for these receptors.

  DOI：

  10.1021/jm00126a007