N'-叔丁基-D-鸟氨酸 | 184576-63-4

• 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
• 中文名称: N'-叔丁基-D-鸟氨酸
• 英文名称: (R)-2-amino-5-(tert-butoxycarbonylamino)pentanoic acid
• 英文别名: N⁵-(tert-butoxycarbonyl)-D-ornithine；(R)-N-Boc-ornithine；D-H-Orn(Boc)-OH；N^δ-Boc-D-ornithine；N^δ-Boc-D-Orn；Nδ-Boc-D-ornithine；(R)-2-Amino-5-((tert-butoxycarbonyl)amino)pentanoic acid；(2R)-2-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid
• CAS: 184576-63-4
• 化学式: C₁₀H₂₀N₂O₄
• 分子量: 232.28
• InChiKey: GLZZMUULAVZVTA-SSDOTTSWSA-N

物化性质

• 沸点：
  401.5±40.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924199090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N'-叔丁基-D-鸟氨酸 在 N-甲基吗啉 、 ammonium hydroxide 、 sodium hydroxide 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 34.51h， 生成 N¹-benzoyl-N⁴-Boc-D-ornithine amide
  参考文献：
  名称：

  d-Amino Acid-Based Protein Arginine Deiminase Inhibitors: Synthesis, Pharmacokinetics, and in Cellulo Efficacy

  摘要：

  The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Because D-amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of D-amino acid analogues of our Pan-PAD inhibitor Cl-amicline, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that D-Cl-amidine and D-o-F-amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of D-Cl-amidine were moderately improved over those of L-Cl-amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.

  DOI：

  10.1021/ml300288d

文献信息

• [18F]Fluoroethyltriazolyl Monocyclam Derivatives as Imaging Probes for the Chemokine Receptor CXCR4
  作者：Alejandro Amor-Coarasa、James M. Kelly、Pradeep K. Singh、Shashikanth Ponnala、Anastasia Nikolopoulou、Clarence Williams、Yogindra Vedvyas、Moonsoo M. Jin、J. David Warren、John W. Babich

  DOI：10.3390/molecules24081612

  日期：——

  Determining chemokine receptor CXCR4 expression is significant in multiple diseases due to its role in promoting inflammation, cell migration and tumorigenesis. [68Ga]Pentixafor is a promising ligand for imaging CXCR4 expression in multiple tumor types, but its utility is limited by the physical properties of 68Ga. We screened a library of >200 fluorine-containing structural derivatives of AMD-3465

  由于其在促进炎症、细胞迁移和肿瘤发生方面的作用，确定趋化因子受体 CXCR4 的表达在多种疾病中具有重要意义。[68Ga]Pentixafor 是一种很有前景的配体，可用于在多种肿瘤类型中对 CXCR4 表达进行成像，但其效用受到 68Ga 物理特性的限制。我们筛选了超过 200 种 AMD-3465 含氟结构衍生物的库，以确定通过正电子发射断层扫描 (PET) 对 CXCR4 表达进行体内成像的有希望的候选者。含有氟乙基三唑的化合物始终获得更高的对接分数。其中六个得分较高的化合物通过点击化学进行放射性标记，并在 PC3-CXCR4 细胞和带有双侧 PC3-WT 和 PC3-CXCR4 异种移植肿瘤的 BALB/c 小鼠中进行评估。配体的表观CXCR4亲和力相对较低，但肿瘤摄取是 CXCR4 特异性的。[18F]RPS-534 (7.2 ± 0.3 %ID/g) 和 [18F]RPS-547
• Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes
  作者：Caterina Camodeca、Elisa Nuti、Francesca Tosetti、Alessandro Poggi、Cristina D'Arrigo、Maria Raffaella Zocchi、Armando Rossello

  DOI：10.1002/cmdc.201800482

  日期：2018.10.8

  we synthesized bioactive fluorescent probes suitable for cell imaging and that are able to specifically target ADAM10 or ADAM17. Two previously developed ADAM17‐ and ADAM10‐selective inhibitors were chosen for conjugation, respectively, to a Cy5.5 dye and to Cy5.5 and FITC dyes. Herein we also report the synthesis of a gold‐labeled compound as an additional bioimaging probe for ADAM10. The newly synthesized

  甲d isintegrin一个第二米etalloproteinase（ADAMs）是膜结合的金属蛋白酶，负责各种跨膜蛋白的胞外域脱落，并在多个相关的生物学过程中发挥重要作用。它们的表达改变与几种病理状况有关，尤其是在各种形式的癌症中都发现了ADAM10或ADAM17过表达。为了更好地了解它们在细胞环境中的调控方式，通过分子成像技术可视化特定的ADAM途径非常有用。为此，我们合成了适用于细胞成像并且能够特异性靶向ADAM10或ADAM17的生物活性荧光探针。选择了两种先前开发的ADAM17和ADAM10选择性抑制剂分别与Cy5.5染料，Cy5.5和FITC染料结合。在这里，我们还报告了金标记化合物的合成，作为ADAM10的另一种生物成像探针。发现新合成的配体在体外对人重组ADAM10和/或ADAM17有活性，显示出IC在纳摩尔范围内具有50个值，并且相对于基质金属蛋白酶（MMP）具有良好的选
• Cyclopentapeptide derivatives and uses thereof
  申请人：Demmer Oliver

  公开号：US09266924B2

  公开（公告）日：2016-02-23

  The present invention, among others, relates to a compound having a structure according to formula (I) or a pharmaceutically acceptable salt thereof, wherein Xaa1 to Xaa4 are independently of each other, an optionally N-alkylated natural or unnatural amino acid, R is H or methyl, L is a linker moiety, Ar is a spacer comprising an aromatic moiety, and D comprises, preferably is i) a combination of an organic complexation agent and a detectable label; or ii) a detectable label, an organic complexation agent or an active substance, said active substance particularly being selected from cytotoxic agents, lipids, sugars, sugar conjugates, sugar derivatives, proteins and combinations thereof, with the proviso that -L-Ar-D does not comprise a 18F-benzoyl residue.

  本发明涉及一种具有以下结构的化合物或其药学上可接受的盐，其中Xaa1至Xaa4彼此独立，为可选择的N-烷基化的天然或非天然氨基酸，R为H或甲基，L为连接基，Ar为包含芳香基团的间隔物，D包括，优选地为i) 有机络合剂和可检测标记的组合；或ii) 可检测标记、有机络合剂或活性物质，所述活性物质特别选自细胞毒性剂、脂质、糖类、糖类结合物、糖类衍生物、蛋白质及其组合，但须注意-L-Ar-D不包含18F-苯甲酰残基。
• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Development of a fluorogenic ADAMTS-7 substrate
  作者：Salvatore Santamaria、Frederic Buemi、Elisa Nuti、Doretta Cuffaro、Elena De Vita、Tiziano Tuccinardi、Armando Rossello、Steven Howell、Shahid Mehmood、Ambrosius P. Snijders、Rens de Groot

  DOI：10.1080/14756366.2021.1983808

  日期：2021.1.1

  reported so far. Screening of inhibitors has been hindered by the lack of a suitable peptide substrate and, consequently, a convenient activity assay. Here we describe the first fluorescence resonance energy transfer (FRET) substrate for ADAMTS-7, ATS7FP7. ATS7FP7 was used to measure inhibition constants for the endogenous ADAMTS-7 inhibitor, TIMP-4, as well as two hydroxamate-based zinc chelating inhibitors

   抽象的 细胞外蛋白酶 ADAMTS-7 已被确定为动脉粥样硬化和冠状动脉疾病 (CAD) 等相关疾病的潜在治疗靶点。但迄今为止，ADAMTS-7抑制剂尚未见报道。由于缺乏合适的肽底物，因此阻碍了抑制剂的筛选，因此也阻碍了方便的活性测定。在这里，我们描述了 ADAMTS-7 的第一个荧光共振能量转移 (FRET) 底物 ATS7FP7。 ATS7FP7 用于测量内源性 ADAMTS-7 抑制剂 TIMP-4 以及两种异羟肟酸锌螯合抑制剂的抑制常数。这些抑制常数与我们的 SDS-PAGE 测定获得的 IC 50值非常匹配，该测定使用潜在 TGF-β 结合蛋白 4 (LTBP4S-A) 的 N 末端片段作为底物。我们的新型荧光底物 ATS7FP7 适用于 ADAMTS-7 抑制剂的高通量筛选，从而加速旨在抑制 ADAMTS-7 作为动脉粥样硬化和 CAD 等心血管疾病的新型治疗方法的转化研究。