tert-butyl (2-((4-fluorophenyl)amino)-2-oxoethyl)carbamate

• 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-butyl (2-((4-fluorophenyl)amino)-2-oxoethyl)carbamate
• 英文别名: tert-butyl N-{[(4-fluorophenyl)carbamoyl]methyl}carbamate；tert-butyl N-[2-(4-fluoroanilino)-2-oxoethyl]carbamate
• 化学式: C₁₃H₁₇FN₂O₃
• mdl: MFCD24391774
• 分子量: 268.288
• InChiKey: YAPXLKXBUCBBRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-((4-fluorophenyl)amino)-2-oxoethyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 2-(4-bromophenoxy)-N-[(4-fluorophenylcarbamoyl)methyl]acetamide
  参考文献：
  名称：

  In silico and pharmacological screenings identify novel serine racemase inhibitors

  摘要：

  D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.

  DOI：

  10.1016/j.bmcl.2014.07.003
• 作为产物：
  描述：

  BOC-甘氨酸 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 18.08h， 生成 tert-butyl (2-((4-fluorophenyl)amino)-2-oxoethyl)carbamate
  参考文献：
  名称：

  Synthesis of analogues of the benzodiazepine Ro 5-3335, antagonist of Tat HIV-1. Biological evaluation by Luciferase transactivation and anti-viral assay

  摘要：

  Ro 5-3335 is a benzodiazepine which is an antagonist of the Tat protein of HIV-1. A series of Ro 5-3335-derived compounds have been synthesized in order to evaluate whether opened analogues of the benzodiazepine tricyclic structure possess biological activity. The analogues are constituted by two aromatic rings variously substituted, linked by an amino acid. The activity of these compounds has been determined by the quantification of both inhibition of Tat activity using a cell-based transfection assay and inhibition of HIV replication in acutely infected cells. No analogue provided a notable inhibition of Tat-dependent transactivation or any anti-HIV activity.

  DOI：

  10.1016/0223-5234(96)85171-3

文献信息

• New isoleucine derived dipeptides as antiprotozoal agent: Synthesis, in silico and in vivo studies.
  作者：Ogechi C. Ekoh、Uchechukwu C. Okoro、Rafat Ali、David I. Ugwu、Sunday N. Okafor、James A. Ezugwu

  DOI：10.1016/j.molstruc.2021.130017

  日期：2021.5

  aceturate. In the antimalarial study, 11b was the most active compound, even better than the standard. Molecular docking result suggests good interaction between the reported compounds and the target protein. The results of haematological analysis, liver and kidney function tests showed that the compounds had no adverse effect on the blood and organs. Compound 11b stands out among the derivatives haven shown

  疟疾耐药性寄生虫的出现越来越多，锥虫病的有效化学疗法不足，代表了热带地区传染病治疗的巨大挑战。关于开发有效的抗原生动物剂，通过使用肽偶联剂将化合物（10）与（8a-j）缩合，合成了十种新的甘草二肽磺酰胺衍生物。化合物11b，11i和11j最能清除11b小鼠的锥虫布氏锥虫，并具有与醋酸二米那嗪相当的活性。在抗疟疾研究中，11b是活性最高的化合物，甚至优于标准化合物。分子对接结果表明所报道的化合物与靶蛋白之间具有良好的相互作用。血液学分析，肝和肾功能测试的结果表明该化合物对血液和器官没有不良影响。化合物11b在衍生物中脱颖而出，这些衍生物在抗疟和抗锥虫试验中均显示出更好的活性。
• Design and synthesis of novel diamide derivatives of glycine as antihyperglycemic agents
  作者：Radhika Sharma、Shubhangi S. Soman

  DOI：10.1080/00397911.2016.1203435

  日期：2016.8.2

  in the market contain a proline mimetic active pharmacophore. Herein, we report the design, synthesis, and preliminary evaluation of a series of novel diamide derivatives of glycine, devoid of the proline mimic, for the treatment of T2D. As predicted from in silico studies, the diamide derivatives of glycine exhibited comparable DPP-4 inhibition with the standard as confirmed by the preliminary in vitro

  摘要 DPP-4 抑制是治疗 2 型糖尿病 (T2D) 的最广泛探索的方法之一。市场上的大多数 DPP-4 抑制剂都含有模拟脯氨酸的活性药效团。在此，我们报告了一系列新型甘氨酸二酰胺衍生物的设计、合成和初步评估，不含脯氨酸模拟物，用于治疗 T2D。正如计算机模拟研究所预测的那样，甘氨酸的二酰胺衍生物表现出与标准品相当的 DPP-4 抑制作用，正如初步体外研究所证实的那样。发现化合物 6b 是该系列合成的所有分子中最有效的 (IC50 94.82 nM) DPP-4 抑制剂。图形概要
• New glycine derived peptides bearing benzenesulphonamide as an antiplasmodial agent
  作者：Daniel Izuchukwu Ugwuja、Uchechukwu Okoro、Shubhanji Soman、Akachukwu Ibezim、David Ugwu、Rina Soni、Bonaventure Obi、James Ezugwu、Ogechi Ekoh

  DOI：10.1039/d0nj04387g

  日期：——

  boc-glycine (4) and different amines using peptide coupling reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt), with triethyl amine and dichloromethane (DCM) as solvents. The target compounds were prepared by reacting compounds 3a–c with compounds 5a–h in the presence of coupling reagents to get twenty four (24) different compounds. The

  在热带地区，疟疾是发展中国家最严重的传染病之一。不久前发现青蒿素抗疟药是抗击疟疾的一项重大突破。但是，最近有关连青蒿素联合治疗耐药的报道都令人担忧，并导致寻找新的化学药物来维持抗击疟疾的能力。在超过25％的商业化学治疗剂中，羧酰胺功能已被证明是重要的药效团。在适当的苯磺酰氯（1a–c）和丙氨酸（2）在碱性水溶液中反应制得了三种苯甲酰胺（3a–c）。八个叔还使用肽偶联剂，例如1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐（EDC）和肽偶联剂，使市售的boc-甘氨酸（4）与不同的胺反应，制得了丁基丁基-氧代-乙基氨基甲酸酯（5a-h）。1-羟基苯并三唑（HOBt），以三乙胺和二氯甲烷（DCM）为溶剂。通过使化合物3a–c与化合物5a–h反应来制备目标化合物在偶联剂的存在下得到二十四（24）种不同的化合物。表征化合物并评估其抗血浆活性。计算的分子描述符和评估的生化参数表明该化合物是药物样且安
• Flexible Fragment Growing Boosts Potency of Quorum‐Sensing Inhibitors against <i>Pseudomonas aeruginosa</i> Virulence
  作者：Michael Zender、Florian Witzgall、Alexander Kiefer、Benjamin Kirsch、Christine K. Maurer、Andreas M. Kany、Ningna Xu、Stefan Schmelz、Carsten Börger、Wulf Blankenfeldt、Martin Empting

  DOI：10.1002/cmdc.201900621

  日期：2020.1.17

  optimization of 2-aminopyridine derivatives as a novel lead-like structure for the treatment of the dangerous opportunistic pathogen Pseudomonas aeruginosa. We pursue an innovative treatment strategy by interfering with the Pseudomonas quinolone signal (PQS) quorum sensing (QS) system leading to an abolishment of bacterial pathogenicity. Our compounds act on the PQS receptor (PqsR), a key transcription

  领先的优化是药物发现中的关键阶段。在这里，我们报告基于片段的发现和优化的2-氨基吡啶衍生物作为一种新型的铅样结构，用于治疗危险的机会性病原体铜绿假单胞菌。我们通过干扰假单胞菌喹诺酮信号（PQS）群体感应（QS）系统来追求创新的治疗策略，从而消除细菌致病性。我们的化合物作用于PQS受体（PqsR），PQSR是控制各种致病性决定因素表达的关键转录因子。在这种目标驱动的方法中，我们利用了通过表面等离振子共振（SPR）进行的生物物理筛选，然后进行了等温滴定量热（ITC）的焓效率（EE）评估。命中优化然后涉及生长载体的鉴定和开发。令人惊讶的是，后者通过引入柔性接头而不是刚性基序而成功实现，从而导致对靶受体的活性和抗毒力增强。
• Approaches to design non-covalent inhibitors for human granzyme B (hGrB)
  作者：Mi-Sun Kim、Lauriane A. Buisson、Dean A. Heathcote、Haipeng Hu、D. Christopher Braddock、Anthony G. M. Barrett、Philip G. Ashton-Rickardt、James P. Snyder

  DOI：10.1039/c4ob01874e

  日期：——

  A structure-based design campaign for non-covalent small molecule inhibitors of human granzyme B was carried out by means of a virtual screening strategy employing three constraints and probe site-mapping with FTMAP to identify ligand “hot spots”. In addition, new scaffolds of diverse structures were subsequently explored with ROCS shape-based superposition methods, following by Glide SP docking, induced fit docking and analysis of QikProp molecular properties. Novel classes of moderately active small molecule blockers (≥25 μM IC50 values) from commercially available libraries were identified, and three novel scaffolds have been synthesized by multi-step procedures. Furthermore, we provide an example of a comprehensive structure-based drug discovery approach to non-covalent inhibitors that relies on the X-ray structure of a covalently bound ligand and suggest that the design path may be compromised by alternative and unknown binding poses.

  针对人类颗粒酶B的非共价小分子抑制剂进行了一项基于结构的设计活动，采用了一种虚拟筛选策略，结合三个约束条件和FTMAP探针位点映射，以识别配体“热点”。此外，随后利用ROCS基于形状的叠加方法探索了多样结构的新骨架，接着进行了Glide SP对接、诱导适合对接及QikProp分子性质分析。识别出来自商业可获取库的新型中等活性小分子拮抗剂（IC50值≥25 μM），并通过多步骤合成了三种新骨架。此外，我们提供了一个全面的结构基础药物发现方法的例子，用于非共价抑制剂，该方法依赖于共价结合配体的X射线结构，并指出设计路径可能会因替代和未知的结合姿势而受到影响。