(2S,4R)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester | 185304-19-2

• 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: (2S,4R)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester
• 英文别名: 2-O-benzyl 1-O-tert-butyl (2S,4R)-4-azidopyrrolidine-1,2-dicarboxylate
• CAS: 185304-19-2
• 化学式: C₁₇H₂₂N₄O₄
• 分子量: 346.386
• InChiKey: NNBVAZYHYUBQCU-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester 在 palladium on activated charcoal 氢气 、 sodium carbonate 、 potassium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 19.0h， 生成 (2S,4R)-4-Amino-1-[2-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-acetyl]-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  N中的合成α - （嘌呤基/嘧啶基乙酰基）-4-氨基脯氨酸非对映体在合成PNA潜在用途

  摘要：

  本文介绍了一种方法，该方法是通过亚甲基桥接同一单元中的乙二胺和甘氨酸组分，从而将构象约束和手性引入PNA主链，从而生成基于4-氨基脯氨酰基主链的PNA，在C-4和C-2上具有手性。以胸腺嘧啶（T）为侧链核碱基（3a-d）的所有四个非对映异构体的合成和表征，以及与四个核碱基（10-13）中的每一个相连的立体异构体之一（2 S，4 R）的合成是描述。使用这些单体单元，可以得到两个模型二聚体（17，18）包含四个手性中心，但仅在一个位点的立体化学不同，并且这些CD数据表明在这些中手性骨架引起的碱基堆积有相当大的结构差异。

  DOI：

  10.1016/0040-4020(96)00924-6
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-cis-4-chloro-L-proline Benzyl Ester 以 N-甲基乙酰胺 、 正己烷 、 水 、 乙酸乙酯 为溶剂， 生成 (2S,4R)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester
  参考文献：
  名称：

  Novel peptides as NS3-serine protease inhibitors of hepatitis C virus

  摘要：

  本发明揭示了具有HCV蛋白酶抑制活性的新型肽化合物，以及制备这些化合物的方法。在另一实施方案中，本发明揭示了包含这些肽段的药物组合物，以及使用它们治疗与HCV蛋白酶相关疾病的方法。

  公开号：

  US20030036501A1

文献信息

• [EN] ARGINASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE L'ARGINASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2019159120A1

  公开（公告）日：2019-08-22

  Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase, wherein R1 is -NHR1a; R1a is -H or -C(O)CH(R1b)NHR1c; and R1b is selected from -H, -(C1-C4 ) alkyl and CH2OR1d and R1cis -H; or R1b and R1c, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1d is H or -CH3.

  化合物的结构式（Ia）或其药学上可接受的盐已被披露，包括化合物的结构式（Ia）的药物组合物以及使用它们用于治疗癌症或呼吸道炎症性疾病和抑制精氨酸酶的方法，其中R1为-NHR1a；R1a为-H或-C（O）CH（R1b）NHR1c；R1b从-H，-（C1-C4）烷基和CH2OR1d中选择，R1c为-H；或R1b和R1c与它们附着的原子一起形成5-成员杂环环；R1d为H或-CH3。
• NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Saksena Anil K.

  公开号：US20110117057A1

  公开（公告）日：2011-05-19

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明披露了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明披露了包含这些化合物的制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Strategies for the Solid-Phase Diversification of Poly-<scp>l</scp>-proline-Type II Peptide Mimic Scaffolds and Peptide Scaffolds Through Guanidinylation
  作者：Stevenson Flemer、Alexander Wurthmann、Ahmed Mamai、José S. Madalengoitia

  DOI：10.1021/jo8012258

  日期：2008.10.3

  A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pinc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH(2)Cl(2) followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.
• Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues
  作者：Franca Zanardi、Paola Burreddu、Gloria Rassu、Luciana Auzzas、Lucia Battistini、Claudio Curti、Andrea Sartori、Giuseppe Nicastro、Gloria Menchi、Nicoletta Cini、Anna Bottonocetti、Silvia Raspanti、Giovanni Casiraghi

  DOI：10.1021/jm701214z

  日期：2008.3.1

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.
• Design and Synthesis of Photoaffinity-Labeling Ligands of the <scp>l</scp>-Prolyl-<scp>l</scp>-leucylglycinamide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor
  作者：Abigail Fisher、Amandeep Mann、Vaneeta Verma、Nancy Thomas、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm050644n

  日期：2006.1.1

  Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D-2 receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity-labeling ligands were designed and synthesized on the basis of the gamma-lactam PLG peptidomimetic 1. The 4-azidobenzoyl and 4-azido-2-hydroxybenzoyl photoaffinity-labeling moieties were placed at opposite ends of PLG peptidomimetic I to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [H-3]-N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were crosslinked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity-labeling agents are binding at the same allosteric site as PLG and PLG peptidomimetic 1.