N-[(R)-1,2-dithiolane-3-pentanoyl]-L-aspartyl-glycine | 341969-23-1

• 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: N-[(R)-1,2-dithiolane-3-pentanoyl]-L-aspartyl-glycine
• 英文别名: N-lipoyl-L-aspartylglycine；N-[5-(3R)-1,2-Dithiolan-3-yl-1-oxopentyl]-L-I+/--aspartylglycine；(3S)-4-(carboxymethylamino)-3-[5-[(3R)-dithiolan-3-yl]pentanoylamino]-4-oxobutanoic acid
• CAS: 341969-23-1
• 化学式: C₁₄H₂₂N₂O₆S₂
• 分子量: 378.47
• InChiKey: XEYZMZFJSAVFBX-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.86
• 重原子数：
  24.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  132.8
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  R-(+)-硫辛酸 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 生成 N-[(R)-1,2-dithiolane-3-pentanoyl]-L-aspartyl-glycine
  参考文献：
  名称：

  Lipoic acid analogs with enhanced pharmacological activity

  摘要：

  Lipoic acid (1,2-dithiolane-3-pentanoic acid) is a pharmacophore with unique antioxidant and cytoprotective properties. We synthesized a library based upon the condensation of natural and unnatural amino acids with the carboxylic acid moiety of lipoic acid. SAR studies were conducted using a cardiac ischemia-reperfusion animal model. Cytoprotective efficacy was associated with the R-enantiomer of the dithiolane. Potency of library compounds was dictated by the acidic strength of the adduct. alpha-N-[(R)1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine, designated CMX-2043, was chosen for further pharmacologic evaluation. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.057

文献信息

• Formulations Comprising Lipoyl Compounds
  申请人：Ischemix, LLC

  公开号：US20150329519A1

  公开（公告）日：2015-11-19

  Provided herein are aqueous pharmaceutical formulations comprising monomeric lipoyl compounds, such as compounds of Structural Formula I: The formulations comprise a lipoyl compound comprising at least one acidic substituent; and an inorganic base in an amount sufficient to deprotonate each acidic substituent in the lipoyl compound. In certain embodiments, the formulations have a pH of from about 6.5 to about 8.0 and a tonicity of from about 250 mOsm to about 350 mOsm.

  本文提供了含有单体脂硫醇化合物的水性制药配方，例如结构式I中的化合物：这些配方包括至少含有一个酸性取代基的脂硫醇化合物；以及足以去质子化脂硫醇化合物中的每个酸性取代基的无机碱。在某些实施方式中，这些配方的pH值约为6.5至8.0，渗透压约为250 mOsm至350 mOsm。
• [EN] FORMULATIONS COMPRISING LIPOYL COMPOUNDS<br/>[FR] FORMULATIONS COMPRENANT DES COMPOSÉS DE LIPOYLE
  申请人：ISCHEMIX LLC

  公开号：WO2015174948A1

  公开（公告）日：2015-11-19

  Provided herein are aqueous pharmaceutical formulations comprising lipoyl compounds, such as compounds of Structural Formula (I): The formulations comprise a lipoyl compound comprising at least one acidic substituent; and an inorganic base in an amount sufficient to deprotonate each acidic substituent in the lipoyl compound. In certain embodiments, the formulations have a pH of from about 6.5 to about 8.0 and a tonicity of from about 250 mOsm to about 350 mOsm.

  本文提供的是含有脂酰化合物的水性制药配方，例如结构式（I）中的化合物：这些配方包括含有至少一个酸性取代基的脂酰化合物；以及足够量的无机碱，用于去质子化脂酰化合物中的每个酸性取代基。在某些实施例中，这些配方的pH值约为6.5至8.0，渗透压约为250 mOsm至350 mOsm。
• Compositions and methods for treating traumatic brain injury
  申请人：Ischemix LLC

  公开号：US10744115B2

  公开（公告）日：2020-08-18

  The present invention relates, in certain embodiments, to methods for preventing and/or treating neurodegenerative damage (e.g., secondary cascade of neurodegenerative damage) and improving functional outcomes (e.g., outcomes associated with cognitive, behavior and sensorimotor function) caused by traumatic brain injury using neuroprotective lipoyl compounds. The present invention also provides, in various embodiments, compositions for use in treating and/or preventing TBI in a subject in need thereof, compounds for use in the manufacture of a medicament for treating and/or preventing TBI in a subject in need thereof, and methods of preparing a pharmaceutical composition for treating and/or preventing secondary brain damage caused by TBI.

  在某些实施方案中，本发明涉及使用神经保护性脂酰基化合物预防和/或治疗由创伤性脑损伤引起的神经退行性损伤（例如，继发性神经退行性损伤级联）和改善功能结果（例如，与认知、行为和感觉运动功能相关的结果）的方法。在各种实施方案中，本发明还提供了用于治疗和/或预防有需要的受试者的创伤性脑损伤的组合物、用于制造治疗和/或预防有需要的受试者的创伤性脑损伤的药物的化合物，以及制备治疗和/或预防创伤性脑损伤引起的继发性脑损伤的药物组合物的方法。
• Substrate Analogues Entering the Lipoic Acid Salvage Pathway via Lipoate-Protein Ligase 2 Interfere with Staphylococcus aureus Virulence
  作者：Albertina Scattolini、Konstantinos Grammatoglou、Anna Nikitjuka、Aigars Jirgensons、María Cecilia Mansilla、Björn Windshügel

  DOI：10.1021/acsinfecdis.4c00148

  日期：2024.6.14

  Lipoic acid (LA) is an essential cofactor in prokaryotic and eukaryotic organisms, required for the function of several multienzyme complexes such as oxoacid dehydrogenases. Prokaryotes either synthesize LA or salvage it from the environment. The salvage pathway in Staphylococcus aureus includes two lipoate-protein ligases, LplA1 and LplA2, as well as the amidotransferase LipL. In this study, we intended

  硫辛酸 (LA) 是原核和真核生物中必需的辅助因子，是多种多酶复合物（例如含氧酸脱氢酶）发挥功能所必需的。原核生物要么合成LA，要么从环境中回收它。金黄色葡萄球菌的补救途径包括两种硫辛酸蛋白连接酶 LpLA1 和 LpLA2，以及酰胺转移酶 LipL。在这项研究中，我们打算通过 LA 类似物劫持补救途径，这些类似物通过 LpLA2 和 LipL 转移到各种脱氢酶的 E2 亚基，从而产生无功能的酶，最终损害细菌的活力。最初，进行了虚拟筛选活动来鉴定与 LpLA2 结合的潜在 LA 类似物。三种选定的化合物影响基本培养基中金黄色葡萄球菌USA300 的生长，浓度范围为 2.5 至 10 μg/mL。对最有效的化合物 ( Lpl-004 ) 的进一步分析表明，它转移到脱氢酶复合物的 E2 亚基上，并对其功能产生负面影响。通过添加硫辛酸依赖性酶复合物的产物可以恢复Lpl-004处理引起的生长障碍。
• Compositions And Methods For Treating Traumatic Brain Injury
  申请人：Ischemix, LLC

  公开号：US20200352904A1

  公开（公告）日：2020-11-12

  The present invention relates, in certain embodiments, to methods for preventing and/or treating neurodegenerative damage (e.g., secondary cascade of neurodegenerative damage) and improving functional outcomes (e.g., outcomes associated with cognitive, behavior and sensorimotor function) caused by traumatic brain injury using neuroprotective lipoyl compounds. The present invention also provides, in various embodiments, compositions for use in treating and/or preventing TBI in a subject in need thereof, compounds for use in the manufacture of a medicament for treating and/or preventing TBI in a subject in need thereof, and methods of preparing a pharmaceutical composition for treating and/or preventing secondary brain damage caused by TBI.