(S)-3-Amino-N-phenethyl-succinamic acid benzyl ester | 108279-23-8

• 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-Amino-N-phenethyl-succinamic acid benzyl ester
• 英文别名: H-Asp(Bzl)-CONH-CH2CH2Ph；benzyl (3S)-3-amino-4-oxo-4-(2-phenylethylamino)butanoate
• CAS: 108279-23-8
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: XSHTXRMUSTWBDN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-Amino-N-phenethyl-succinamic acid benzyl ester 在 10percent Pd/C 氢气 、 三乙胺 作用下， 以 甲醇 、 乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 BOC-Trp-L-3-(2-naphthyl)alanyl-Asp-2-phenylethylamide
  参考文献：
  名称：

  Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists

  摘要：

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.

  DOI：

  10.1021/jm000937a
• 作为产物：
  描述：

  2-苯乙胺 在 三氟乙酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 生成 (S)-3-Amino-N-phenethyl-succinamic acid benzyl ester
  参考文献：
  名称：

  Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists

  摘要：

  The two hormones cholecystokinin and gastrin share the same C-terminal sequence of amino acids, namely Gly(29)-Trp(30)-Met(31)-Asp(32)-Phe(33)-NH2. Nevertheless, this congruence has not precluded using this structure to develop selective ligands for either CCK1 or CCK2 receptors. Manipulation of the hydrophobic residues at positions 31 and 33 gave a series of CCK1 tripeptide antagonists, typified by N-t-BOC-Trp-2-Nal-Asp-2-(phenyl)ethylamide (pK(B) 6.8 +/- 0.3). Molecular modeling was used to identify the bioactive conformation of these CCK1-selective compounds and prompted the design of new peptoid structures. We aimed to maintain the conformation of the parent series by exploiting patterns of hydrogen-bonding and pi-stacking interactions present in the original molecule, rather than introducing additional covalent bonds. The prototype, N-(succinyl-o-Asp-2-phenylethylamido)-L-Trp-2-( 2-naphthyl) ethylamide, was a potent and selective CCK1 antagonist (pK(B) 7.2 +/- 0.3). Furthermore, the new series showed patterns of biological activity that mirrored those of the parent tripeptides. These compounds contain elements of both peptide primary and secondary structure and represent a novel approach to designing peptidomimetics. Interesting results were obtained from comparing models of a representative tripeptide CCK1 antagonist with a conformation of CCK30-33 that others have proposed to be responsible for its activity at the CCK2 receptor. The results suggest that CCK1 and CCK2 receptors recognize enatiomeric dispositions of the Trp(30) indole, Asp(32) carboxylic acid, and C-terminal phenyl groups arrayed about a common backbone configuration. This "functional chirality" may underpin the mechanism by which these closely related receptor systems bind CCK30-33 and explain patterns of selectivity observed with optical isomers of a number of peptoid and nonpeptide ligands.

  DOI：

  10.1021/jm000937a
• 作为试剂：
  描述：

  (tert-Butoxycarbonyl)-β-benzyl-L-aspartic acid 2-phenylethylamide 、 苄磺酰氯 在 ice 、 盐酸 、 (S)-3-Amino-N-phenethyl-succinamic acid benzyl ester 、 二氯甲烷 、 三乙胺 、 碳酸氢钠 、 Brine 、 magnesium sulfate 作用下， 以 乙酸乙酯 、 二氯甲烷 为溶剂， 反应 16.5h， 以to yield the product as a white solid (51 mg, 42%)的产率得到PhCH2SO2-Asp-CONH-CH2CH2Ph
  参考文献：
  名称：

  Tripeptide &agr;-ketoamides

  摘要：

  一种新型三肽α-酮酰胺类化合物，适用于选择性抑制丝氨酸蛋白酶、选择性抑制半胱氨酸蛋白酶、普遍抑制所有丝氨酸蛋白酶和普遍抑制所有半胱氨酸蛋白酶，化学式为M1-AA-AA-AA-CO-NR3R4。

  公开号：

  US06235929B1

文献信息

• Derivatives of aspartic acid and glutamic acid having
  申请人：James Black Foundation Limited

  公开号：US05399748A1

  公开（公告）日：1995-03-21

  Arylsulfonamide derivatives of .alpha.-amino dicarboxylic acids such as aspartic acid and glutamic acid posses anti-cholecystokinin activity. They are useful in the treatment of cholecystokinin-related disorders such as anorexia nervosa, pancreatic inflammation, biliary tract disease, Zollinger-Ellison syndrome and various psychiatric disorders, as well as in the potentiation of opiate analgesia, and in the treatment of certain cancers.

  阿烷磺酰胺衍生物的α-氨基二羧酸，例如天冬氨酸和谷氨酸，具有抗胆囊收缩素活性。它们在治疗胆囊收缩素相关疾病，如厌食症，胰腺炎，胆道疾病，Zollinger-Ellison综合征和各种精神障碍方面非常有用，同时可以增强阿片类镇痛剂的镇痛作用，并用于治疗某些癌症。