(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-乙基-33-[(E,1R,2R)-1-羟基-2-甲基己-4-烯基]-1,4,7,10,12,15,19,25,28-九甲基-6,9,18-三(2-甲基丙基)-3,21,24-三(丙-2-基)-1,4,7,10,13,16,19,22,25,28,31-十一氮杂环三十三烷-2,5,8,11,14,17,20,23,26,29,32-十一酮 | 159605-70-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-乙基-33-[(E,1R,2R)-1-羟基-2-甲基己-4-烯基]-1,4,7,10,12,15,19,25,28-九甲基-6,9,18-三(2-甲基丙基)-3,21,24-三(丙-2-基)-1,4,7,10,13,16,19,22,25,28,31-十一氮杂环三十三烷-2,5,8,11,14,17,20,23,26,29,32-十一酮
• 英文名称: N-methyl-4-valine-cyclosporin
• 英文别名: [MeVal]4-CsA；[N-MeVal]-4-cyclosporin；N-MeVal-4-cyclosporin；PKF220-384；MeVal4Cs；[MeVal]⁴-cyclosporin；N-Methyl-valyl-4-cyclosporin A；(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21,24-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
• CAS: 159605-70-6
• 化学式: C₆₁H₁₀₉N₁₁O₁₂
• 分子量: 1188.6
• InChiKey: UUDGYAWEAWOYIK-UJUZIFHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  84
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  279
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(2-二甲基铵基乙基二硫基)乙基-二甲基铵二氯化物 、 (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-乙基-33-[(E,1R,2R)-1-羟基-2-甲基己-4-烯基]-1,4,7,10,12,15,19,25,28-九甲基-6,9,18-三(2-甲基丙基)-3,21,24-三(丙-2-基)-1,4,7,10,13,16,19,22,25,28,31-十一氮杂环三十三烷-2,5,8,11,14,17,20,23,26,29,32-十一酮 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 [(R)-2-(N,N-dimethylamino)ethylthio-Sar]-3-[NMeVal]-4-cyclosporin
  参考文献：
  名称：

  Cyclosporin derivatives for the treatment and prevention of a viral infection

  摘要：

  本发明涉及一种化合物，其化学式为（I）或其药用可接受的盐，其中符号如规范中定义；包括相同化合物的药物组合物，以及使用相同化合物治疗或预防病毒感染的方法。

  公开号：

  US09217015B2
• 作为产物：
  描述：

  Boc-N-甲基-L-缬氨酸 在 2,4,6-三甲基吡啶 、 sodium methylate 、 1-丙基磷酸酐 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 71.5h， 生成 (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-乙基-33-[(E,1R,2R)-1-羟基-2-甲基己-4-烯基]-1,4,7,10,12,15,19,25,28-九甲基-6,9,18-三(2-甲基丙基)-3,21,24-三(丙-2-基)-1,4,7,10,13,16,19,22,25,28,31-十一氮杂环三十三烷-2,5,8,11,14,17,20,23,26,29,32-十一酮
  参考文献：
  名称：

  Cyclosporin derivatives for the treatment and prevention of a viral infection

  摘要：

  本发明涉及一种化合物，其化学式为（I）或其药用可接受的盐，其中符号如规范中定义；包括相同化合物的药物组合物，以及使用相同化合物治疗或预防病毒感染的方法。

  公开号：

  US09217015B2

文献信息

• Synthesis and neurotrophic activity of nonimmunosuppressant cyclosporin A derivatives
  作者：Ling Wei、Joseph P Steiner、Gregory S Hamilton、Yong-Qian Wu

  DOI：10.1016/j.bmcl.2004.06.028

  日期：2004.9

  exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results suggest that neurotrophic activity of cyclosporin A and its derivatives resides in the binding domain

  为了利用亲环蛋白作为神经病学药物设计的潜在靶标，我们在本演示中证明了环孢菌素A的几种非免疫抑制剂类似物（在“效应子”域的各个位置进行了修饰）与环孢菌素A相比是等价的神经生长剂。结果表明，环孢菌素A及其衍生物的神经营养活性位于结合域中，并且与亲环蛋白的结合和/或抑制旋转异构酶活性可能是亲环蛋白配体神经营养作用的必要条件。
• NOVEL CYCLOSPORIN DERIVATIVES FOR THE TREATMENT AND PREVENTION OF A VIRAL INFECTION
  申请人：Su Zhuang

  公开号：US20130303438A1

  公开（公告）日：2013-11-14

  The present invention relates to a compound of the formula (I): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing a viral infection using the same.

  本发明涉及公式（I）的化合物或其药学上可接受的盐，其中符号如规范中所定义; 包含相同化合物的制药组合物，使用相同化合物治疗或预防病毒感染的方法。
• NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF
  申请人：S&T Global Inc.

  公开号：US20130210704A1

  公开（公告）日：2013-08-15

  The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.

  本发明涉及公式(I)的化合物或其药学上可接受的盐，其中符号如规范中所定义；以及包含该化合物的制药组合物，用于治疗或预防病毒感染、炎症、干眼症、中枢神经系统疾病、心血管疾病、癌症、肥胖症、糖尿病、肌肉营养不良和脱发的方法。
• NOVEL CYCLOSPORIN DERIVATIVES FOR THE TREATMENT AND PREVENTION OF VIRAL INFECTIONS
  申请人：S&T Global Inc.

  公开号：US20150111815A1

  公开（公告）日：2015-04-23

  The present invention relates to a compound of formula (I): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same; a method for treating or preventing a viral infection using the same.
• COMPOUNDS THAT PARTICIPATE IN COOPERATIVE BINDING AND USES THEREOF
  申请人：Warp Drive Bio, LLC

  公开号：US20160199506A1

  公开（公告）日：2016-07-14

  The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity. In some embodiments, the compounds of the invention “re-program” the binding of the presenter proteins to protein targets that either do not normally bind to the presenter protein (e.g., do not show detectable binding in mammalian cells absent the compound). In some embodiments, provided compounds “re-program” presenter protein binding to greatly enhance interaction with a particular target with which it may have some interaction absent the compound. Interactions achieved through such reprogramming result in an ability to modulate the activity of these new targets.