threonine butyrate | 1256239-22-1

• 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: threonine butyrate
• 英文别名: L-threonine butyrate；O-butyryl L-threonine；(2S,3R)-O-(n-butanoyl)-L-threonine；(2S,3R)-2-amino-3-butanoyloxybutanoic acid
• CAS: 1256239-22-1
• 化学式: C₈H₁₅NO₄
• 分子量: 189.211
• InChiKey: GYYRWHJBQFNPNW-VDTYLAMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  L-苏氨酸 、 丁酰氯 在 三氟乙酸 、 三乙胺 作用下， 以 水 为溶剂， 反应 12.5h， 以96%的产率得到threonine butyrate
  参考文献：
  名称：

  Simple and inexpensive threonine-based organocatalysts for the highly diastereo- and enantioselective direct large-scale syn-aldol and anti-Mannich reactions of α-hydroxyacetone

  摘要：

  Simple and inexpensive threonine-based organocatalysts that promote syn-aldol reactions and three-component asymmetric anti-Mannich reactions of alpha-hydroxyacetone achieving a respectable level of enantioselectivities are reported. The syn-aldol products could be obtained with up to a 99:1 syn/anti ratio and > 99% ee while the anti-Mannich products could be obtained with up to a 96:4 anti/syn ratio and > 99% ee. Catalyst 1c can be used efficiently on a large-scale with the enantioselectivities of the syn-aldol and anti-Mannich reactions being maintained at the same level, which offers a great possibility for application in industry. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.06.022

文献信息

• [EN] ANTI-MICROBIAL AGENT-POLYMER CONJUGATES AND METHODS OF USE THEREOF<br/>[FR] CONJUGUÉS D'AGENT ANTIMICROBIEN-POLYMÈRE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2018195078A1

  公开（公告）日：2018-10-25

  The present disclosure provides a conjugate comprising an anti-microbial agent and a hydrophilic polymer; and compositions, including pharmaceutical compositions, comprising the conjugates. The present disclosure provides a conjugate comprising a polymyxin covalently linked to a maltodextrin polymer; and compositions, including pharmaceutical compositions, comprising the conjugates. The present disclosure provides methods of inhibiting growth of a bacterium, and methods of treating a bacterial infection.

  本公开提供了一种包含抗微生物剂和亲水性聚合物的共轭物；以及包括药物组合物在内的组合物。本公开提供了一种包含共价连接到麦芽糖聚合物的多粘菌素的共轭物；以及包括药物组合物在内的组合物。本公开提供了抑制细菌生长的方法，以及治疗细菌感染的方法。
• POLYMYXIN DERIVATIVES AND USES THEREOF
  申请人：VAARA Martti Sakari

  公开号：US20090215677A1

  公开（公告）日：2009-08-27

  The present invention relates to a polymyxin derivative wherein R1, R2 and R3 are optional and R1, R2, R3, R5, R8 and R9 are cationic or neutral amino acid residues selected so that the total number of positive charges at physiological pH is at least two but no more than three; and to a combination product comprising at least two such derivatives. The invention further relates to a method for treating, alleviating or ameliorating an infection in a subject, caused by a Gram-negative bacterium by administering a therapeutically effective amount of a derivative according to the present invention to said subject; to a method for sensitizing Gram-negative bacteria to an antibacterial agent by administering, simultaneously or sequentially in any order a therapeutically effective amount of said antibacterial agent and a derivative according to the present invention to said subject; to methods for developing novel antibiotics; for reducing the nephrotoxicity, for improving the pharmacokinetic properties of natural polymyxins and octapeptins; and for sensitizing clinically important bacteria to a host defense mechanism complement present in serum. Finally, the invention relates to a process for preparing such polymyxin derivatives.

  本发明涉及一种聚霉素衍生物，其中R1，R2和R3是可选的，而R1、R2、R3、R5、R8和R9是阳离子或中性氨基酸残基，选定这些残基使得在生理pH下正电荷总数至少为两个但不超过三个；以及包含至少两种这种衍生物的组合物。本发明还涉及一种通过向受体内给予本发明所述的衍生物的治疗有效量来治疗、缓解或改善由革兰氏阴性菌引起的感染的方法；一种通过同时或顺序给予治疗有效量的抗菌药物和本发明所述的衍生物来使革兰氏阴性菌对抗菌药物敏感的方法；一种开发新型抗生素的方法；降低天然聚霉素和八肽霉素的肾毒性，改善其药代动力学特性的方法；以及使临床重要细菌对存在于血清中的宿主防御机制补体敏感的方法。最后，本发明涉及一种制备这种聚霉素衍生物的方法。
• SHORT FATTY ACID TAIL POLYMYXIN DERIVATIVES AND USES THEREOF
  申请人：VAARA Martti Sakari

  公开号：US20090239792A1

  公开（公告）日：2009-09-24

  The present invention relates to a polymyxin derivative wherein the derivative has a total of three positive charges at physiological pH and wherein the terminal moiety (D) of the derivative comprises a total of 1 to 5 carbon atoms; and to a combination product comprising at least two such derivatives. The invention further relates to a method for sensitizing Gram-negative bacteria to an antibacterial agent by administering, simultaneously or sequentially in any order a therapeutically effective amount of said antibacterial agent and a derivative according to the present invention to said subject; to methods for developing novel antibiotics; and for sensitizing clinically important bacteria to a host defense mechanism complement present in serum. The invention also relates to a method of treating a subject for a gram-negative bacterial infection by administering a polymyxin derivative of the invention in combination with a second antibacterial agent. Finally, the invention relates to a process for preparing such polymyxin derivatives.

  本发明涉及一种聚霉素衍生物，其中该衍生物在生理pH下具有总共三个正电荷，且该衍生物的末端基团（D）包括总共1至5个碳原子；以及包含至少两种这样的衍生物的组合物。本发明还涉及一种方法，通过同时或顺序给予所述抗菌剂和本发明的衍生物的治疗有效量来使革兰氏阴性菌对抗菌剂敏感；用于开发新型抗生素的方法；以及使临床重要细菌对存在于血清中的宿主防御机制补体敏感的方法。本发明还涉及一种治疗革兰氏阴性细菌感染的方法，通过给予本发明的聚霉素衍生物与第二种抗菌剂的组合物来治疗受试者。最后，本发明涉及一种制备这样的聚霉素衍生物的方法。
• [EN] SHORT FATTY ACID TAIL POLYMYXIN DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE POLYMYXINE À QUEUE ACIDE GRAS COURT ET LEURS UTILISATIONS
  申请人：NORTHERN ANTIBIOTICS OY

  公开号：WO2009098357A1

  公开（公告）日：2009-08-13

  The present invention relates to a polymyxin derivative wherein the derivative has a total of three positive charges at physiological pH and wherein the terminal moiety (D) of the derivative comprises a total of 1 to 5 carbon atoms; and to a combination product comprising at least two such derivatives. The invention further relates to a method for sensitizing Gram-negative bacteria to an antibacterial agent by administering, simultaneously or sequentially in any order a therapeutically effective amount of said antibacterial agent and a derivative according to the present invention to said subject; to methods for developing novel antibiotics; and for sensitizing clinically important bacteria to a host defense mechanism complement present in serum. The invention also relates to a method of treating a subject for a gram-negative bacterial infection by administering a polymyxin derivative of the invention in combination with a second antibacterial agent. Finally, the invention relates to a process for preparing such polymyxin derivatives.

  本发明涉及一种聚霉素衍生物，其中在生理pH下，该衍生物具有总共三个正电荷，且该衍生物的末端基团（D）包含1至5个碳原子；以及包含至少两种这样的衍生物的组合产品。本发明还涉及一种方法，通过同时或顺序给予治疗有效量的抗菌剂和本发明的衍生物，使革兰氏阴性细菌对抗菌剂敏感；用于开发新型抗生素的方法；以及使临床重要细菌对存在于血清中的宿主防御机制互补体敏感的方法。本发明还涉及一种通过给予本发明的聚霉素衍生物与第二种抗菌剂联合治疗受革兰氏阴性细菌感染的方法。最后，本发明涉及一种制备这种聚霉素衍生物的方法。
• Polymyxin derivatives and uses thereof
  申请人：Vaara Martti Sakari

  公开号：US20080287345A1

  公开（公告）日：2008-11-20

  The present invention relates to a polymyxin derivative wherein R1, R2 and R3 are optional and R1, R2, R3, R5, R8 and R9 are cationic or neutral amino acid residues selected so that the total number of positive charges at physiological pH is at least two but no more than three; and to a combination product comprising at least two such derivatives. The invention further relates to a method for treating, alleviating or ameliorating an infection in a subject, caused by a Gram-negative bacterium by administering a therapeutically effective amount of a derivative according to the present invention to said subject; to a method for sensitizing Gram-negative bacteria to an antibacterial agent by administering, simultaneously or sequentially in any order a therapeutically effective amount of said antibacterial agent and a derivative according to the present invention to said subject; to methods for developing novel antibiotics; for reducing the nephrotoxicity, for improving the pharmacokinetic properties of natural polymyxins and octapeptins; and for sensitizing clinically important bacteria to a host defence mechanism complement present in serum. Finally, the invention relates to a process for preparing such polymyxin derivatives.