O-benzylaspartyl-phenylalanine amide | 5609-55-2

• 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: O-benzylaspartyl-phenylalanine amide
• 英文别名: H-Asp(OBzl)-Phe-NH2；Asp(OBzl)PheNH2；β-O-Benzyl-Asp-Phe-amid；(β-Benzyl)-Asp-Phe-amid；benzyl (3S)-3-amino-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate
• CAS: 5609-55-2
• 化学式: C₂₀H₂₃N₃O₄
• 分子量: 369.42
• InChiKey: VXVTVVBBRWMNNV-IRXDYDNUSA-N

物化性质

• 熔点：
  99-100 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  678.8±55.0 °C(Predicted)
• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O-benzylaspartyl-phenylalanine amide 在 盐酸 、 palladium 10% on activated carbon 、 甲酸铵 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 生成 五肽胃泌素
  参考文献：
  名称：

  Microwave-assisted solution phase peptide synthesis in neat water

  摘要：

  在微波辐射下，使用TBTU/HOBt/DIEA作为耦合组合，在纯水中开发了一种环境友好的溶液相多肽合成方法。该方法的关键特点包括替代常见的毒性有机溶剂如DMF和NMP，使用更少的反应物，与N-α-Boc保护和N-α-Fmoc保护的氨基酸以及所有常用侧链保护基团兼容，反应时间短，且在高效和高纯度下实现无消旋合成。

  DOI：

  10.1039/c3ra43040e
• 作为产物：
  描述：

  CBZ-L-天门冬氨酸β-苄酯 在 氢溴酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 O-benzylaspartyl-phenylalanine amide
  参考文献：
  名称：

  多肽。第三部分 胃泌素C端四肽序列，其旋光异构体和酰化衍生物的合成

  摘要：

  的合成所描述的，通过各种途径，的大号-trytophyl-大号-methionyl-大号-aspartyl-大号-苯丙氨酸酰胺，以及此四肽酰胺和它的各种酰化衍生物d，d，d，d - ，d，大号，L，L-，L，D，L，L-，L，L，D，L-，L，L，L，D-大号，d，d，d - ，大号，大号，d，d - ，d，大号，d，d - ，和d，d，大号，大号-异构体。

  DOI：

  10.1039/j39660000555

文献信息

• Structure-Based Design of New Constrained Cyclic Agonists of the Cholecystokinin CCK-B Receptor
  作者：Armand G. S. Blommaert、Hélène Dhôtel、Bertrand Ducos、Christiane Durieux、Nathalie Goudreau、André Bado、Christiane Garbay、Bernard P. Roques

  DOI：10.1021/jm9603072

  日期：1997.2.1

  New constrained cyclic pseudopeptide cholecystokinin-B (CCK-B) agonists have been designed on the basis of conformational characteristics of the potent and selective CCK-B agonist Boc-Trp-(NMe)Nle-Asp-Phe-NH2 (K-i = 0.8 nm, selectivity ratio CCK-A/CCK-B > 6000) (Goudreau et al. Biopolymers, 1994, 34, 155-169). These compounds are among the first successful examples of macrocyclic constrained CCK4 analogs endowed with agonist properties and as such may be of value for the development of nonpeptide CCK-B agonists. The affinities and selectivities of these compounds for CCK-B and CCK-A receptors have been determined in vitro by measuring the displacement of [H-3]pCCK(8) binding to guinea pig cortex and pancreas membranes, respectively. The most potent compound, 8b, N-(cycloamido)-alpha-Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH2, has a K-i value of 15 +/- 1 nM for guinea pig cortex membranes with a good CCK-B selectivity ratio (CCK-A/CCK-B = 147). Furthermore, 8b behaved as a potent and full agonist in a functional assay which measures the stimulation of inositol phosphate accumulation in CHO cells transfected with the rat CCK-B receptor (EC(50) = 7 nM). The in vivo affinity of 8b for mouse brain CCK-B receptors was determined following intracerebroventricular injection (ID50 similar to 29 nmol/kg). 8b was also shown to cross the blood-brain barrier (0.16%), after intravenous administration in mice. 8b also increased gastric acid secretion measured in anesthetized rats after intravenous injection. Therefore, 8b appears to be an interesting pharmacological tool and is currently under investigation as a lead for further development of nonpeptide CCK-B agonists.
• Cerovsky, Vaclav; Pirkova, Jana; Majer, Pavel, Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 7, p. 1873 - 1882
  作者：Cerovsky, Vaclav、Pirkova, Jana、Majer, Pavel、Slaninova, Jirina、Hlavacek, Jan

  DOI：——

  日期：——
• Development of Peptide 3D Structure Mimetics:  Rational Design of Novel Peptoid Cholecystokinin Receptor Antagonists
  作者：Caroline M. R. Low、James W. Black、Howard B. Broughton、Ildiko M. Buck、Jonathan M. R. Davies、David J. Dunstone、Robert A. D. Hull、S. Barret Kalindjian、Iain M. McDonald、Michael J. Pether、Nigel P. Shankley、Katherine I. M. Steel

  DOI：10.1021/jm000937a

  日期：2000.9.1

  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.
• Pseudopeptide CCK-4 analogues incorporating the Ψ[CH(CN)NH] peptide bond surrogate
  作者：Susana Herrero、M.Luisa Suárez-Gea、Rosario González-Muñiz、M.Teresa García-López、Rosario Herranz、Santiago Ballaz、Ana Barber、Ana Fortuño、Joaquín Del Río

  DOI：10.1016/s0960-894x(97)00107-8

  日期：1997.1

  The synthesis, binding to CCK receptors, and in vitro functional activity of pseudopeptide CCK-4 analogues incorporating the (R) or (S) Psi[CH(CN)NH] peptide bond surrogate at the Nle(31)-Asp(32) or Trp(30)-Nle(31) bonds are described. Z-Trp Psi[(S)CH(CN)NH]Nle-Asp-Phe-NH2 retained the high CCK-B receptor binding affinity of Boc-[Nle(31)]-CCK-4, and was a potent and selective CCK-B antagonist in the isolated guinea pig ileum. (C) 1997 Elsevier Science Ltd.
• CEROVSKY, VACLAV;PIRKOVA, JANA;MAJER, PAVEL;SLANINOVA, JIRINA;HLAVACEK, J+, COLLECT. CZECHOSL. CHEM. COMMUN., 55,(1990) N, C. 1873-1882
  作者：CEROVSKY, VACLAV、PIRKOVA, JANA、MAJER, PAVEL、SLANINOVA, JIRINA、HLAVACEK, J+

  DOI：——

  日期：——