benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[(2S,5S,8R,17R)-5-butyl-2-[(4-hydroxyphenyl)methyl]-17-[(2-methylpropan-2-yl)oxycarbonylamino]-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-oxobutanoate | 120085-39-4

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[(2S,5S,8R,17R)-5-butyl-2-[(4-hydroxyphenyl)methyl]-17-[(2-methylpropan-2-yl)oxycarbonylamino]-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-oxobutanoate
• CAS: 120085-39-4
• 化学式: C₆₈H₈₉N₁₁O₁₄
• 分子量: 1284.52
• InChiKey: ASIGFLGPADJVOP-URYQCRIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  93
• 可旋转键数：
  29
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  377
• 氢给体数：
  12
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[(2S,5S,8R,17R)-5-butyl-2-[(4-hydroxyphenyl)methyl]-17-[(2-methylpropan-2-yl)oxycarbonylamino]-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-oxobutanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以92%的产率得到(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[(2S,5S,8R,17R)-5-butyl-2-[(4-hydroxyphenyl)methyl]-17-[(2-methylpropan-2-yl)oxycarbonylamino]-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-oxobutanoic 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：

  Nle-Asp(OBzl)-Phe-NH2 TFA salt 、 (S)-2-{[(2S,5S,8R,17R)-17-tert-Butoxycarbonylamino-5-butyl-2-(4-hydroxy-benzyl)-3,6,14,18-tetraoxo-1,4,7,13-tetraaza-cyclooctadecane-8-carbonyl]-amino}-3-(1H-indol-3-yl)-propionic acid 在 N-羟基丁二酰亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[(2S,5S,8R,17R)-5-butyl-2-[(4-hydroxyphenyl)methyl]-17-[(2-methylpropan-2-yl)oxycarbonylamino]-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-oxobutanoate
  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

文献信息

• CHARPENTIER, B.;DOR, A.;ROY, P.;ENGLAND, P.;PHAM, H.;DURIEUX, C., J. MED. CHEM., 32,(1989) N, C. 1184-1190
  作者：CHARPENTIER, B.、DOR, A.、ROY, P.、ENGLAND, P.、PHAM, H.、DURIEUX, C.

  DOI：——

  日期：——