(tert-Butoxycarbonyl)-β-benzyl-L-aspartic acid 2-phenylethylamide | 108279-08-9

• 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: (tert-Butoxycarbonyl)-β-benzyl-L-aspartic acid 2-phenylethylamide
• 英文别名: BOC-Asp(OBn)-2-phenylethylamide；Boc-Asp(Bzl)-NH(CH2)2C6H5；Boc-Asp(Bzl)-CONH-CH2CH2Ph；benzyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-(2-phenylethylamino)butanoate
• CAS: 108279-08-9
• 化学式: C₂₄H₃₀N₂O₅
• 分子量: 426.513
• InChiKey: VUYQPXIWPGMMKB-FQEVSTJZSA-N

物化性质

• 沸点：
  631.7±55.0 °C(Predicted)
• 密度：
  1.152±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (tert-Butoxycarbonyl)-β-benzyl-L-aspartic acid 2-phenylethylamide 在 ice 、 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以to give 22的产率得到(S)-3-Amino-N-phenethyl-succinamic acid benzyl ester
  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
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-苄酯 、 alkaline earth salt of/the/ methylsulfuric acid 在 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 40.0h， 生成 (tert-Butoxycarbonyl)-β-benzyl-L-aspartic acid 2-phenylethylamide
  参考文献：
  名称：

  Studies on Inhibition of Enzymatic Arginyltransfer Reaction.

  摘要：

  体外研究了合成多胺以及天冬氨酸和谷氨酸的各种衍生物对精氨酰-tRNA-蛋白转移酶的抑制活性。所有测试的多胺在 0.1 或 10 mM 的浓度下分别显示出非特异性的激活或抑制作用，这表明多胺与 tRNA 之间存在相互作用。在新制备的活性位点定向化合物（包括迄今报道的抑制肽）中，发现 L-天冬氨酸 α-[(S)-(-)-萘乙基酰胺]对酶活性的抑制作用最强，且有轻微的底物活性，而 R-异构体的抑制作用很弱，从而提供了有关酶活性位点的信息。

  DOI：

  10.1248/cpb.46.1169

文献信息

• Analogues of the Cholecystokinin C-Terminal Tetrapeptide
  作者：Jan Hlaváček、Renáta Marcová、Lenka Maletínská、Jiřina Slaninová

  DOI：10.1135/cccc19942511

  日期：——

  Substituted phenylethyl amides and phenylethyl esters Va - Vj derived from the carboxyterminal tetrapeptide part of the cholecystokinin were synthesized and their biological properties assayed. In the original CCK tetrapeptide structure Trp-Met-Asp-Phe-NH₂ the Met was replaced by Lys(Pamc) and the terminal Phe-NH₂ was replaced by Phe-NHCH₂C₆H₅ or Phe-OCH₂C₆H₅ moiety with a various degree of alkylation in the Ph ring. A bioassay revealed that these simple CCK analogues were selectively bound to A receptors from pancreas, whereas no binding to B receptors from brain was found. Some of the compounds behaved as weak inhibitors of CCK activity on gall bladder and guinea pig ileum contractions without any effect in anorectic assay.

  从胆囊收缩素的羧基末端四肽部分合成了取代苯乙基酰胺和苯乙基酯Va - Vj，对它们的生物学性质进行了测定。在原始的CCK四肽结构Trp-Met-Asp-Phe-NH2中，Met被Lys(Pamc)取代，末端的Phe-NH2被Phe-NHCH2C6H5或Phe-OCH2C6H5取代，苯环中的取代程度不同。生物测定显示，这些简单的CCK类似物选择性地结合到胰腺的A受体，而在大脑中没有发现与B受体的结合。其中一些化合物表现为弱的CCK活性抑制剂，对胆囊和豚鼠回肠的收缩没有影响。
• 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。
• Anti-aggregatory peptides
  申请人：SmithKline Beecham Corporation

  公开号：US05849690A1

  公开（公告）日：1998-12-15

  This invention relates to compounds which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, a method for inhibiting platelet aggregation and clot formation in a mammal, and a method for inhibiting reocclusion of a blood vessel following fibrinolytic therapy.

  本发明涉及对抑制血小板聚集有效的化合物，用于实现此种活性的制药组合物，一种在哺乳动物中抑制血小板聚集和凝块形成的方法，以及一种在纤溶疗法后抑制血管再闭塞的方法。
• Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro
  作者：J. Samanen、F. Ali、T. Romoff、R. Calvo、E. Sorenson、J. Vasko、B. Storer、D. Berry、D. Bennett、M. Strohsacker、D. Powers、J. Stadel、A. Nichols

  DOI：10.1021/jm00114a022

  日期：1991.10.1

  The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575-Arg-Gly-Asp-Ser- and Fg-gamma 400-411-HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1-mu-M [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, K(i) 2.9 +/- 1.9-mu-M (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, K(i) 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N-alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (K(i) 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4-mu-M dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.
• Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue
  作者：M. Rodriguez、P. Fulcrand、J. Laur、A. Aumelas、J. P. Bali、Jean Martinez

  DOI：10.1021/jm00123a003

  日期：1989.3

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.