N-(t-butoxycarbonyl)-L-valyl-L-prolinamide | 107897-23-4

• 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: N-(t-butoxycarbonyl)-L-valyl-L-prolinamide
• 英文别名: Boc-Val-Pro-NH2；Boc-VP-NH2；Boc-L-Val-L-Pro-NH2；tert-butyl N-[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 107897-23-4
• 化学式: C₁₅H₂₇N₃O₄
• 分子量: 313.397
• InChiKey: KVGCCBQHDNCCEB-QWRGUYRKSA-N

物化性质

• 沸点：
  530.7±50.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(t-butoxycarbonyl)-L-valyl-L-prolinamide 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 Glp-Val-Pro-NH₂
  参考文献：
  名称：

  促甲状腺激素释放激素类似物的合成。1.促甲状腺激素释放活性中枢神经系统作用完全分离。

  摘要：

  合成了在位置2主要包含脂肪族氨基酸的二十四种促甲状腺激素释放激素（TRH）类似物，并测试了其中枢神经系统（CNS）和激素（TSH）的活性。五氟苯基酯方法在合成中的应用导致了最佳收率和高纯度的产物。具有三元或四元直链或支链烷基侧链的中性三肽pGlu-Nva-Pro-NH2（9），pGlu-Nle-Pro-NH2（10）和pGlu-Leu-Pro-NH2（3）中央氨基酸位置的抗癫痫作用比TRH强2.5至10倍，表明组氨酸的存在对于CNS活性不是必需的。与TRH相比，类似物9表现出十倍的抗过敏活性，并且发现其在释放TSH方面完全没有活性。

  DOI：

  10.1021/jm00372a006
• 作为产物：
  描述：

  N-Boc-L-缬氨酸 、 L-脯氨酰胺盐酸盐 在 1-羟基苯并三唑 、 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87%的产率得到N-(t-butoxycarbonyl)-L-valyl-L-prolinamide
  参考文献：
  名称：

  Opioid Activities of Morphiceptin Analogs Derived from Human β-Casein

  摘要：

  合成了四种含有N端Tyr–Pro序列的四肽酰胺，它们可能是由人β-酪蛋白降解产生的可能与阿片受体结合的物质。当这些肽用于测试它们结合大鼠脑μ和δ阿片受体的能力时，仅H–Tyr–Pro–Phe–Val-NH2有活性，与来自牛β-酪蛋白的吗啡酰肽(H–Tyr–Pro–Phe–Pro–NH2)相比，它对μ受体具有60%的亲和力增加。它也像吗啡酰肽一样具有很高的μ选择性，μ/δ选择性比为285。其他三个类似物，H–Tyr–Pro–Ser–Phe–NH2、H–Tyr–Pro–Val–Arg–NH2 和 H–Tyr–Pro–Val–Pro–NH2，几乎完全无活性。这些结果表明，对于类似吗啡酰肽的四肽酰胺，在第3位存在Phe对于引发与μ阿片受体的结合活性至关重要。通过测量圆二色谱光谱进行的构象分析表明，四肽酰胺序列 Tyr–Pro–Xxx–Pro(或Val)–NH2 是与μ阿片受体相互作用的重要结构要求。

  DOI：

  10.1246/bcsj.63.1753

文献信息

• Opioid Activities of Morphiceptin Analogs Derived from Human β-Casein
  作者：Kazuyasu Sakaguchi、Hiroshi Sakamoto、Yoshiko Tsubaki、Michinori Waki、Tommaso Costa、Yasuyuki Shimohigashi

  DOI：10.1246/bcsj.63.1753

  日期：1990.6

  Four tetrapeptide amides with the N-terminal Tyr–Pro sequence were synthesized as possible opioid agonists that can be produced by degradation of human β-casein. When these peptides were tested for their ability to bind to the μ and δ opioid receptors in rat brain, only H–Tyr–Pro–Phe–Val-NH2 was active, showing the 60% increased affinity for the μ receptors as compared with morphiceptin (H–Tyr–Pro–Phe–Pro–NH2) derived from bovine β-casein. It was highly μ-selective, as well as morphiceptin, with the μ/δ-selectivity ratio of 285. Other three analogs, H–Tyr–Pro–Ser–Phe–NH2, H–Tyr–Pro–Val–Arg–NH2 and H–Tyr–Pro–Val–Pro–NH2, were almost completely inactive. These results suggested that, for the morphiceptin-like tetrapeptide amides, the presence of Phe at position 3 is essential to elicit an activity to bind to the μ opioid receptors. Conformational considerations by measuring the CD spectra indicated that the sequence of tetrapeptide amide Tyr–Pro–Xxx–Pro(or Val)–NH2 is an important structural requirement to interact with the μ opioid receptors.

  合成了四种含有N端Tyr–Pro序列的四肽酰胺，它们可能是由人β-酪蛋白降解产生的可能与阿片受体结合的物质。当这些肽用于测试它们结合大鼠脑μ和δ阿片受体的能力时，仅H–Tyr–Pro–Phe–Val-NH2有活性，与来自牛β-酪蛋白的吗啡酰肽(H–Tyr–Pro–Phe–Pro–NH2)相比，它对μ受体具有60%的亲和力增加。它也像吗啡酰肽一样具有很高的μ选择性，μ/δ选择性比为285。其他三个类似物，H–Tyr–Pro–Ser–Phe–NH2、H–Tyr–Pro–Val–Arg–NH2 和 H–Tyr–Pro–Val–Pro–NH2，几乎完全无活性。这些结果表明，对于类似吗啡酰肽的四肽酰胺，在第3位存在Phe对于引发与μ阿片受体的结合活性至关重要。通过测量圆二色谱光谱进行的构象分析表明，四肽酰胺序列 Tyr–Pro–Xxx–Pro(或Val)–NH2 是与μ阿片受体相互作用的重要结构要求。
• 1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(<i>S</i>)-pyrrolidine:  A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties
  作者：Edwin B. Villhauer、John A. Brinkman、Goli B. Naderi、Bryan F. Burkey、Beth E. Dunning、Kapa Prasad、Bonnie L. Mangold、Mary E. Russell、Thomas E. Hughes

  DOI：10.1021/jm030091l

  日期：2003.6.1

  Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728

  抑制二肽基肽酶IV（DPP-IV）可能成为2型糖尿病的有价值的治疗方法。描述了新型DPP-IV抑制剂类N-取代的甘氨酰-2-氰基吡咯烷类化合物的合成与构效关系，以及从临床开发化合物1- [2- [5-氰基吡啶-2]开始的途径-基）氨基]乙基氨基]乙酰基-2-氰基-（S）-吡咯烷（NVP-DPP728，8c）进行后续研究，[1-[[（（3-羟基-1-金刚烷基）氨基]乙酰基] -2 -氰基-（S）-吡咯烷（NVP-LAF237，12j）。讨论了肥胖Zucker fa / fa大鼠中12j的药理学特征以及正常食蟹猴中8c和12j的药代动力学特征。结果表明12j是有效，稳定，
• Selective, Tight-Binding Inhibitors of Integrin α4β1 That Inhibit Allergic Airway Responses
  作者：Ko-chung Lin、Humayun S. Ateeq、Sherry H. Hsiung、Lillian T. Chong、Craig N. Zimmerman、Alfredo Castro、Wen-cherng Lee、Charles E. Hammond、Sandhya Kalkunte、Ling-Ling Chen、R. Blake Pepinsky、Diane R. Leone、Andrew G. Sprague、William M. Abraham、Alan Gill、Roy R. Lobb、Steven P. Adams

  DOI：10.1021/jm980673g

  日期：1999.3.1

  development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.

  整联蛋白α4beta1介导白细胞募集，激活，介质释放和凋亡抑制，并且它在炎症病理生理学中发挥着核心作用。描述了基于来自细胞纤连蛋白交替剪接的连接段1（CS-1）肽的Leu-Asp-Val（LDV）序列的高亲和力，选择性的alpha4beta1抑制剂，该抑制剂采用了新型N端肽“上限”策略。一种抑制剂BIO-1211的效价比起始肽高约10（6）倍，并表现出紧密结合的特性（koff = 1.4 x 10（-4）s-1，KD = 70 pM），这是一个了不起的发现用于蛋白质受体的非共价小分子抑制剂。BIO-1211对激活形式的alpha4beta1也具有200倍的选择性，并且它刺激整联蛋白beta1亚基上配体诱导的表位的表达，与受体的配体结合位点的占有率一致的性质。用3毫克雾化剂量的BIO-1211预处理过敏羊可抑制抗原攻击后的早期和晚期气道反应，并防止非特异性气道对卡巴胆碱的过度反应。这些结果表
• Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors
  作者：C. Robin Ganellin、Paul B. Bishop、Ramesh B. Bambal、Suzanne M. T. Chan、Bertrand Leblond、Andrew N. J. Moore、Lihua Zhao、Pierre Bourgeat、Christiane Rose、Froylan Vargas、Jean-Charles Schwartz

  DOI：10.1021/jm0500830

  日期：2005.11.1

  The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + GlyTrp-Met-Asp-Phe-NH(2). Starting from Val-Pro-NHBu, a dipeptide of submicromolar affinity that had previously been generated to serve as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18, K(i) = 80 nM). Further transformation (by making a benzologue) gave the indoline analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity (Ki = 7 nM). Retrospective analysis suggested the possibility of a general approach to designing exopeptidase inhibitors starting from the structure of the first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe-NHBu (37), but this only had K(i) = 9.4 mu M. Molecular modeling, to determine the minimum energy conformations and explain the 1000-fold better affinity of butabindide, indicated that 37 cannot access the likely active conformation of butabindide.
• SAKAGUCHI, KAZUYASU;SAKAMOTO, HIROSHI;TSUBAKI, YOSHIKO;WAKI, MICHINORI;CO+, BULL. CHEM. SOC. JAP., 63,(1990) N, C. 1753-1757
  作者：SAKAGUCHI, KAZUYASU、SAKAMOTO, HIROSHI、TSUBAKI, YOSHIKO、WAKI, MICHINORI、CO+

  DOI：——

  日期：——