(S)-3-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[3-(2-methoxy-phenyl)-ureido]-hexanoylamino}-N-((S)-1-carbamoyl-2-phenyl-ethyl)-succinamic acid | 130408-76-3

• 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: (S)-3-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[3-(2-methoxy-phenyl)-ureido]-hexanoylamino}-N-((S)-1-carbamoyl-2-phenyl-ethyl)-succinamic acid
• 英文别名: Boc-Trp-hCit(Ph(2-OMe))(Ph(2-OMe))-Asp-Phe-NH2；(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-6-[(2-methoxyphenyl)carbamoylamino]hexanoyl]amino]-4-oxobutanoic acid
• CAS: 130408-76-3
• 化学式: C₄₃H₅₄N₈O₁₀
• 分子量: 842.949
• InChiKey: FIGISBJSOVEARM-CUPIEXAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  61
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  272
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  BOC-L-色氨酸羟基琥珀酰亚胺酯 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 54.0h， 生成 (S)-3-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[3-(2-methoxy-phenyl)-ureido]-hexanoylamino}-N-((S)-1-carbamoyl-2-phenyl-ethyl)-succinamic acid
  参考文献：
  名称：

  Minor Structural Differences in Boc-CCK-4 Derivatives Dictate Affinity and Selectivity for CCK-A and CCK-B Receptors

  摘要：

  We previously reported novel Boc-CCK-4 (Boc-Trp-Met-Asp-Phe-NH2) derivatives possessing the general structure Boc-Trp-Lys[N-epsilon-CO-NH-(R-Ph)]-Asp-Phe-NH2 (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842). In contrast to Boc-CCK-4, which is 70-fold selective for the CCK-B receptor, the modified lysine-bearing tetrapeptides were highly potent and selective full agonists at the CCK-A receptor. Further investigation of the structure-activity profile following modification of the substituted phenylurea moiety appended off the lysine revealed that moving certain substituents, e.g. nitro or acetyl, from the 2- or 3-position on the phenyl ring to the 4-position, a relatively minor and subtle structural modification within the tetrapeptide, resulted in loss of CCK-A receptor selectivity and development of a trend toward CCK-B selectivity. These tetrapeptides, e.g. Boc-Trp-Lys[N-epsilon-CO-NH-(4-NO2-Ph)]-Asp-Phe-NH2 and Boc-Trp-Lys[N-epsilon-CO-NH-(4-Ac-Ph)]-Asp-Phe-NH2, were full agonists relative to CCK-8 in stimulating intracellular calcium mobilization in a cell line that expresses the, CCK-B receptor.

  DOI：

  10.1021/jm960509y

文献信息

• Boc-CCK-4 derivatives containing side-chain ureas as potent and selective CCK-A receptor agonists
  作者：Kazumi Shiosaki、Chun Wel Lin、Hana Kopecka、Michael D. Tufano、Bruce R. Bianchi、Thomas R. Miller、David G. Witte、Alex M. Nadzan

  DOI：10.1021/jm00113a023

  日期：1991.9

  derivatives were communicated recently as having high potency and selectivity for the CCK-A receptor (Shiosaki et al. J. Med. Chem. 1990, 33, 2950-2952). While Boc-CCK-4 binds selectively to the CCK-B receptor, replacement of the methionine with an N epsilon-substituted lysine dramatically reversed receptor selectivity, leading to the development of this novel series of tetrapeptides. A detailed structure-activity

  最近公开了新型Boc-CCK-4衍生物，其具有对CCK-A受体的高效力和选择性（Shiosaki等人，J.Med.Chem.1990，33，2950-2952）。当Boc-CCK-4选择性结合CCK-B受体时，用Nε取代的赖氨酸替代甲硫氨酸可显着逆转受体选择性，从而导致了这一新颖的四肽系列的发展。以一般结构Boc-Trp-Lys（N epsilon-CO-NHR）-Asp-Phe-NH2表示的一系列脲取代的四肽的详细结构活性分析显示，许多取代的苯基，萘基，赖氨酸侧链上的脂肪族脲残基产生了有效的选择性CCK-A配体。这些四肽在刺激胰淀粉酶释放中引起完全的激动剂反应，其被选择性的CCK-A受体拮抗剂有效地阻断。尿素向硫脲的转化显着降低了CCK-A结合力，用赖氨酸或同源赖氨酸替代赖氨酸也是如此。相对于CCK-8，在磷酸肌醇（PI）水解中作为部分激动剂（功效低于80％）的四肽未在豚鼠痤疮中表现出高剂量抑制淀粉酶分泌的作用。
• Minor Structural Differences in Boc-CCK-4 Derivatives Dictate Affinity and Selectivity for CCK-A and CCK-B Receptors
  作者：Kazumi Shiosaki、Chun Wel Lin、Hana Kopecka、Bruce Bianchi、Thomas Miller、Michael Stashko、David Witte

  DOI：10.1021/jm960509y

  日期：1997.3.1

  We previously reported novel Boc-CCK-4 (Boc-Trp-Met-Asp-Phe-NH2) derivatives possessing the general structure Boc-Trp-Lys[N-epsilon-CO-NH-(R-Ph)]-Asp-Phe-NH2 (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842). In contrast to Boc-CCK-4, which is 70-fold selective for the CCK-B receptor, the modified lysine-bearing tetrapeptides were highly potent and selective full agonists at the CCK-A receptor. Further investigation of the structure-activity profile following modification of the substituted phenylurea moiety appended off the lysine revealed that moving certain substituents, e.g. nitro or acetyl, from the 2- or 3-position on the phenyl ring to the 4-position, a relatively minor and subtle structural modification within the tetrapeptide, resulted in loss of CCK-A receptor selectivity and development of a trend toward CCK-B selectivity. These tetrapeptides, e.g. Boc-Trp-Lys[N-epsilon-CO-NH-(4-NO2-Ph)]-Asp-Phe-NH2 and Boc-Trp-Lys[N-epsilon-CO-NH-(4-Ac-Ph)]-Asp-Phe-NH2, were full agonists relative to CCK-8 in stimulating intracellular calcium mobilization in a cell line that expresses the, CCK-B receptor.