methyl (S)-2-azido-3-(1H-indol-3-yl)propanoate | 1192373-21-9

• 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: methyl (S)-2-azido-3-(1H-indol-3-yl)propanoate
• 英文别名: methyl (2S)-2-azido-3-(1H-indol-3-yl)propanoate
• CAS: 1192373-21-9
• 化学式: C₁₂H₁₂N₄O₂
• 分子量: 244.253
• InChiKey: ORHPNXHEOBIPSK-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-azido-3-(1H-indol-3-yl)propanoate 在 四丁基氟化铵 、 铜 、 copper(II) sulfate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 16.17h， 生成 C₂HF₃O₂*C₃₂H₃₃N₉O₇
  参考文献：
  名称：

  Universal Peptidomimetics

  摘要：

  This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.

  DOI：

  10.1021/ja1071916
• 作为产物：
  描述：

  L-色氨酸甲酯盐酸盐 在 copper(ll) sulfate pentahydrate 、 1-(azidosulfonyl)-1H-imidazol-3-ium tetrafluoroborate 、 potassium hydrogencarbonate 作用下， 以 水 、 乙腈 为溶剂， 以84 %的产率得到methyl (S)-2-azido-3-(1H-indol-3-yl)propanoate
  参考文献：
  名称：

  从伯胺安全生产有机叠氮化物的自动化合成

  摘要：

  本文描述的是利用含有所有所需试剂（包括咪唑-1-磺酰叠氮化物四氟硼酸盐）的预包装胶囊开发一种自动化且可重复的方法，用于将伯胺转化为有机叠氮化物。除了手动将伯胺加载到反应容器中之外，整个反应和产物分离过程可以自动完成，无需用户进一步参与，并以高纯度提供所需的有机叠氮化物。这种实用且简单的基于胶囊的自动化方法提供了一种方便且安全的生成有机叠氮化物的方法，而无需处理或暴露潜在爆炸性试剂。

  DOI：

  10.1021/acs.joc.4c00603

文献信息

• Synthesis, Absorption, and Fluorescence Studies of Coumaryl-Labelled Amino Acids and Dipeptides Linked Via Triazole Ring
  作者：Santosh Kumari、Sunita Joshi、S. M. Abdul Shakoor、Devesh S. Agarwal、Siva S. Panda、Debi D. Pant、Rajeev Sakhuja

  DOI：10.1071/ch14708

  日期：——

  Fluorophores based on 4-triazolyl, 7-hydroxy-4-triazolylmethyl, 4-O-triazolylmethyl, and 7-O-triazolylmethyl coumaryl-tagged amino acids and dipeptides were synthesized by copper-catalyzed [3 + 2] cycloaddition reaction between azido- or alkynyl-functionalized coumarins with alkynyl- or azido-functionalized amino acid and dipeptides in good-to-excellent yields. Steady-state absorption and the fluorescence properties of the synthesized conjugates were studied. The chemical applicability of these amino acid and peptide-based fluorophores was successfully demonstrated by their linear elongation by further tagging them with appropriate C- or N-terminus amino acid.

  通过铜催化叠氮或炔基化香豆素与炔基或叠氮官能化氨基酸和二肽之间的[3 + 2]环加成反应，合成了基于 4-三唑基、7-羟基-4-三唑基甲基、4-O-三唑基甲基和 7-O-三唑基甲基香豆素标记的氨基酸和二肽的荧光团，产率从良好到极佳。研究了合成共轭物的稳态吸收和荧光特性。通过进一步标记适当的 C 端或 N 端氨基酸，这些基于氨基酸和肽的荧光团的线性延伸成功地证明了它们的化学适用性。
• Design, Synthesis, and Activity Evaluation of Stereoconfigured Tartarate Derivatives as Potential Anti-inflammatory Agents <i>In Vitro</i> and <i>In Vivo</i>
  作者：Priya Kumari、Palwinder Singh、Jashanpreet Kaur、Rajbir Bhatti

  DOI：10.1021/acs.jmedchem.1c00880

  日期：2021.7.8

  enzymes suffer from nonoptimal selectivity, in particular for COX-2, we present here the results of purposely designed tartarate derivatives that exhibit favorable selectivity and significant effectiveness against COX-2 and LOX. Integrated approaches of molecular simulation, organic synthesis, and biochemical/physical experiments identified 15 inhibiting COX-2 and LOX with respective IC50 4 and 7 nM

  临床前和临床数据表明，炎症与许多疾病的发病机制密切相关，包括癌症、阿尔茨海默病和糖尿病。炎症级联反应涉及多种细胞因子，最终以 COX-2/LOX 的激活结束，以产生前列腺素和白三烯。虽然这些酶的可用抑制剂具有非最佳选择性，特别是对 COX-2，但我们在此展示了特意设计的酒石酸盐衍生物的结果，这些衍生物对 COX-2 和 LOX 表现出良好的选择性和显着的有效性。分子模拟、有机合成和生化/物理实验的综合方法确定了15 个抑制 COX-2 和 LOX 的化合物，其 IC 504 和 7 纳米。在瑞士白化小鼠5 mg kg –1的剂量下，15在 2-3 小时内逆转了 65% 的痛觉和 33% 的炎症。我们发现实验和模拟之间有很好的一致性，并使用模拟来合理化我们的观察。
• Development of a Potent and Selective HDAC8 Inhibitor
  作者：Oscar J. Ingham、Ronald M. Paranal、William B. Smith、Randolph A. Escobar、Han Yueh、Tracy Snyder、John A. Porco、James E. Bradner、Aaron B. Beeler

  DOI：10.1021/acsmedchemlett.6b00239

  日期：2016.10.13

  A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8.

  通过改变多种化合物的用途，发现了一种新型的，组蛋白脱乙酰基酶8（HDAC8）的同工型选择性抑制剂。药物化学的优化导致鉴定出了一种高效（0.8 nM）的HDAC8选择性抑制剂。
• Modification of the lead molecule: Tryptophan and piperidine appended triazines reversing inflammation and hyeperalgesia in rats
  作者：Priya Kumari、Sukhmeet Kaur、Jashanpreet Kaur、Rajbir Bhatti、Palwinder Singh

  DOI：10.1016/j.bmc.2019.115246

  日期：2020.1

  agent. Selective for COX-2 over COX-1, compound 10 exhibited IC50 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg-1 dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia. As evidenced by the results of molecular modeling studies supported by the nuclear Overhauser enhancement data,

  分子的结构优化使其适合于COX-2的活性位点口袋，占据了与天然底物花生四烯酸覆盖的空间相同的空间，有助于化合物10作为有效的消炎剂的出现。相对于COX-1，CO10-2具有选择性，对COX-2的IC50为0.02 µM，当以10 mg kg-1的剂量使用时，逆转乙酸引起的大鼠炎症反应的发生率为73％，相同剂量的化合物也可以挽救动物从福尔马林的炎症期诱发痛觉过敏。正如核Overhauser增强数据所支持的分子模型研究结果所证明的那样，COX-2活性位点口袋中分子的适当几何结构有助于其与Ser530的氢键/疏水相互作用，
• [EN] ERAP INHIBITORS<br/>[FR] INHIBITEURS D'ERAP
  申请人：UNIV LILLE

  公开号：WO2022129589A1

  公开（公告）日：2022-06-23

  The present disclosure relates to novel compounds of formula (I) which are useful as inhibitors of endoplasmic reticulum aminopeptidases (ERAP), in particular as inhibitors of ERAP2. The disclosure also relates to the therapeutic use of these compounds, in particular the use of these compounds in the treatment or prophylaxis of proliferative disorders, autoinflammatory disorders and autoimmune disorders.

  本公开涉及一种新型化合物，其化学式为（I），可用作内质网氨肽酶（ERAP）的抑制剂，特别是ERAP2的抑制剂。本公开还涉及这些化合物的治疗用途，特别是这些化合物在治疗或预防增生性疾病、自身免疫性疾病和自身免疫性疾病方面的应用。