(2-fluorobenzoyl)-L-phenylalanine

• 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: (2-fluorobenzoyl)-L-phenylalanine
• 英文别名: (2S)-2-[(2-fluorobenzoyl)amino]-3-phenylpropanoic acid
• 化学式: C₁₆H₁₄FNO₃
• 分子量: 287.29
• InChiKey: HCZOUTUSJOQBNE-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-fluorobenzoyl)-L-phenylalanine 在 Hoveyda-Grubbs catalyst second generation 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.15h， 生成 2-fluoro-N-((S)-1-oxo-1-(((S,E)-6-oxo-1-phenylhept-4-en-3-yl)-amino)-3-phenylpropan-2-yl)benzamide
  参考文献：
  名称：

  Optimization Strategy of Novel Peptide-Based Michael Acceptors for the Treatment of Human African Trypanosomiasis

  摘要：

  This paper describes an optimization strategy of the highly active vinyl ketone 3 which was recognized as a strong inhibitor of rhodesain of Trypanosoma brucei rhodesiense, endowed with a k(second) value of 67 X 10(6) M-1 min(-1) coupled with a high binding affinity (K-i = 38 pM). We now report a new structure-activity relationship study based on structural variations on the P3, P2, and P1' sites which led us to identify two potent lead compounds, i.e., vinyl ketones 4h and 4k. Vinyl ketone 4h showed an impressive potency toward rhodesain (k(second) = 8811 X 10(5)) coupled to a good antiparasitic activity (EC50 = 3.6 mu M), while vinyl ketone 4k proved to possess the highest binding affinity toward the trypanosomal protease (K-i = 0.6 pM) and a submicromolar antiparasitic activity (EC50 = 0.67 mu M), thus representing new lead compounds in the drug discovery process for the treatment of Human African Trypanosomiasis.

  DOI：

  10.1021/acs.jmedchem.9b00908
• 作为产物：
  描述：

  C₁₇H₁₆FNO₃ 在 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 12.15h， 生成 (2-fluorobenzoyl)-L-phenylalanine
  参考文献：
  名称：

  Optimization Strategy of Novel Peptide-Based Michael Acceptors for the Treatment of Human African Trypanosomiasis

  摘要：

  This paper describes an optimization strategy of the highly active vinyl ketone 3 which was recognized as a strong inhibitor of rhodesain of Trypanosoma brucei rhodesiense, endowed with a k(second) value of 67 X 10(6) M-1 min(-1) coupled with a high binding affinity (K-i = 38 pM). We now report a new structure-activity relationship study based on structural variations on the P3, P2, and P1' sites which led us to identify two potent lead compounds, i.e., vinyl ketones 4h and 4k. Vinyl ketone 4h showed an impressive potency toward rhodesain (k(second) = 8811 X 10(5)) coupled to a good antiparasitic activity (EC50 = 3.6 mu M), while vinyl ketone 4k proved to possess the highest binding affinity toward the trypanosomal protease (K-i = 0.6 pM) and a submicromolar antiparasitic activity (EC50 = 0.67 mu M), thus representing new lead compounds in the drug discovery process for the treatment of Human African Trypanosomiasis.

  DOI：

  10.1021/acs.jmedchem.9b00908

文献信息

• [EN] ANTIBACTERIAL AGENTS: N(ALPHA)-AROYL-N-ARYL-PHENYLALANINAMIDES<br/>[FR] AGENTS ANTIBACTÉRIENS : N (ALPHA)-AROYL-N-ARYL-PHÉNYLALANINAMIDES
  申请人：UNIV RUTGERS

  公开号：WO2015120320A1

  公开（公告）日：2015-08-13

  The invention provides compounds having activity as bacterial RNA polymerase inhibitors and antibacterial agents, as well as compositions comprising the compounds and methods for their use. Specifically, phenylalanineamide and tyrosinamide compounds are disclosed that have inhibitory activity toward mycobacterium tuberculosis RNA polymerase. Use of these compounds in the treatment o prevention of M. tuberculosis infections in a mammal, is disclosed.

  该发明提供了具有细菌RNA聚合酶抑制剂和抗菌剂活性的化合物，以及包含这些化合物的组合物和它们的使用方法。具体地，揭示了对结核分枝杆菌RNA聚合酶具有抑制活性的苯丙氨酰胺和酪氨酰胺化合物。还揭示了在哺乳动物中使用这些化合物治疗或预防结核分枝杆菌感染的方法。
• Palladium-Catalyzed Aminocarbonylation in Solid-Phase Peptide Synthesis: A Method for Capping, Cyclization, and Isotope Labeling
  作者：Anna Skogh、Stig D. Friis、Troels Skrydstrup、Anja Sandström

  DOI：10.1021/acs.orglett.7b01068

  日期：2017.6.2

  A new synthetic approach for introducing N-capping groups onto peptides attached to a solid support, combining aminocarbonylation under mild conditions using a palladacycle precatalyst and solid-phase peptide synthesis, is reported. The use of a silacarboxylic acid as an in situ CO-releasing molecule allowed the reaction to be performed in a single vial. The method also enables versatile substitution

  报道了一种新的合成方法，该方法用于在结合有固相支持物的肽上引入N封端基团，并在适度条件下使用Palladacycle预催化剂和固相肽合成方法将氨基羰基化结合在一起。使用硅烷羧酸作为原位释放CO的分子使得反应可以在单个小瓶中进行。该方法还可以实现侧链的通用取代，侧链至侧链的环化以及修饰肽的选择性[ 13 C]酰基标记。
• Multi-Institution Research and Education Collaboration Identifies New Antimicrobial Compounds
  作者：Amelia A. Fuller、Amy B. Dounay、Douglas Schirch、Daniel G. Rivera、Karl A. Hansford、Alysha G. Elliott、Johannes Zuegg、Matthew A Cooper、Mark A. T. Blaskovich、Jacob R. Hitchens、Sarah Burris-Hiday、Kristiana Tenorio、Yanira Mendez、J. Geno Samaritoni、Martin J. O’Donnell、William L. Scott

  DOI：10.1021/acschembio.0c00732

  日期：2020.12.18

  implementing Distributed Drug Discovery (D3) programs. This report showcases that a collaborative research and educational process is a powerful approach to discover new molecules inhibiting microbial growth. Educational gains for students engaged in this project are highlighted in parallel to the research advances. Aspects of D3 that contribute to its success, including an emphasis on reproducibility

  迫切需要新的抗生素来解决日益增长的多重耐药性感染。合成了包括五个结构支架的76种不同功能的化合物，并测试了它们抑制微生物生长的能力。26种化合物在开放式抗菌药物发现社区（CO-ADD）的主要表型筛选中显示出活性。活性分子的后续测试证实了两种非天然二肽抑制了新型隐球菌的生长最小抑菌浓度（MIC）≤8μg/ mL。由实施分布式药物发现（D3）计划的五所学校的本科生进行了合成。该报告表明，协作研究和教育过程是发现抑制微生物生长的新分子的有力方法。在研究进展的同时，着重强调了参与该项目的学生的教育收益。讨论了D3有助于其成功的各个方面，包括强调程序的可重复性，以强调该方法解决重要研究问题并为其他结合的化学生物学研究和教学工作提供帮助的力量。
• ANTIBACTERIAL AGENTS: N(ALPHA)-AROYL-N-ARYL-PHENYLALANINAMIDES
  申请人：Rutgers, The State University of New Jersey

  公开号：EP3102193A1

  公开（公告）日：2016-12-14
• US9919998B2
  申请人：——

  公开号：US9919998B2

  公开（公告）日：2018-03-20