吉环孢素 | 74436-00-3

• 物质功能分类: 分析化学 - 对照品
• 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: 吉环孢素
• 英文名称: norvaline-2-cyclosporin
• 英文别名: [Nva²]-CsA；Norvaline-2-Cs；cyclosporine G；Cyclosporin G；geclosporin；CsG；(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-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: 74436-00-3
• 化学式: C₆₃H₁₁₃N₁₁O₁₂
• 分子量: 1216.66
• InChiKey: ZMKGDQSIRSGUDJ-VSROPUKISA-N

物化性质

• 熔点：
  196-197°
• 比旋光度：
  D20 -245° (c = 1.0 in chloroform); D20 -191° (c = 1.04 in methanol)
• 沸点：
  1297.8±65.0 °C(Predicted)
• 密度：
  1.013±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  86
• 可旋转键数：
  16
• 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：

  吉环孢素 在 甲烷磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 17.0h， 以46%的产率得到Isocyclosporin G
  参考文献：
  名称：

  环孢素E，F，G，H和I

  摘要：

  新型环孢菌素E，F，G，H和I的分离和结构测定

  DOI：

  10.1002/hlca.19820650538
• 作为产物：
  描述：

  三乙胺 、 溴 生成 吉环孢素
  参考文献：
  名称：

  CHRISTENSEN, B. G.;JOHNSTON, D. B. R.;SCHMITT, S. M.

  摘要：

  DOI：

文献信息

• Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
  申请人：Counts David F.

  公开号：US10463611B2

  公开（公告）日：2019-11-05

  The present disclosure provides a once-daily water-soluble pharmaceutically active formulation for oral administration. In certain embodiments, the composition comprises a water-soluble pharmaceutically active organic compound incorporated into a small particulate, each particulate having a core of the water-soluble pharmaceutically active organic compound or an acceptable salt thereof in reversible association with a pharmaceutically acceptable drug-binding polymer. The core of the composition being surrounded by an insoluble water permeable membrane that is capable of delaying the dissolution of the pharmaceutically active compound therewithin and providing for extended release of the pharmaceutically active compound. In some embodiments, the formulation of the invention are designed to extend release of the pharmaceutically active organic compound for about 3 hours to about 8 hours, thereby enabling preparation of an extended release formulation for any pharmaceutically active compound with a half-life of from about 16 hours to about 21 hours.

  本公开提供了一种用于口服的每日一次水溶性药用活性制剂。在某些实施方案中，该组合物包括掺入小颗粒中的水溶性药用活性有机化合物，每个颗粒都有一个水溶性药用活性有机化合物或其可接受盐的核心，该核心与药学上可接受的药物结合聚合物可逆结合。组合物的核心由不溶性透水膜包围，该膜能够延迟其中的药用活性化合物的溶解，并延长药用活性化合物的释放时间。在某些实施方案中，本发明的制剂可将药用活性有机化合物的释放时间延长约 3 小时至约 8 小时，从而能够制备半衰期为约 16 小时至约 21 小时的任何药用活性化合物的缓释制剂。
• The Role of Water Molecules in the Structure-Based Design of (5-Hydroxynorvaline)-2-cyclosporin: Synthesis, Biological Activity, and Crystallographic Analysis with Cyclophilin A
  作者：Vincent Mikol、Christos Papageorgiou、Xaver Borer

  DOI：10.1021/jm00017a020

  日期：1995.8

  Analysis of the contact surface of the cyclophilin A (CypA)/cyclosporin A (CsA, 1) crystal structure delineates a unique cavity between both molecules in the vicinity of the Abu-2 side chain atoms of 1 (Abu pocket). Therefore, (5-hydroxynorvaline)-2-cyclosporin (2) was designed and prepared as a CsA derivative which could mediate additional interactions within the pocket. The X-ray crystal structure of the CypA/2 complex at 1.76 Angstrom resolution shows that 1 and 2 have identical backbone conformations and that the introduced hydroxypropyl chain makes indeed the expected supplemental interactions with CypA. However, 2 has 8-9-fold lower binding affinity than 1 for CypA. This results from a presumed unfavorable free energy change associated with the displacement of one of the tightly bound water molecules within the pocket and a change in prebinding equilibria. The role of the later was assessed by comparing the conformation distribution of 1 and 2 to that of norvaline-2-cyclosporin (3) and norvaline-2-(D-MeSer)-3-cyclosporin (4).
• Sequencing of cyclosporins by fast atom bombardment and linked-scan mass spectrometry
  作者：Vladimír Havlíček、Alexandr Jegorov、Petr Sedmera、Miroslav Ryska

  DOI：10.1002/oms.1210281214

  日期：1993.12

  AbstractThe mass spectrometric sequence determination of amino acid residues in cyclosporins using fast atom bombardment, collisionally activated dissociations in the first field‐free region and linked B/E scan is described. The general fragmentation scheme was derived from the spectra of cyclosporins A, B, C, D, F, G, L and [DH‐MeBmt1]CS. The main fragmentation pathways start by primary splitting between amino acids 2–3, 1–11 and 5–6. The corresponding N‐terminal b‐type ions are common fragment types in the mass spectra. The 1–11 splitting can be enhanced by the introduction of a lactone group into the peptide ring by conversion of cyclosporins into isocyclosporins. The fragmentation scheme was used for amino acid sequence determination in four new natural cyclosporins, [MeLeu1]CS, [Leu4]CS, [Ile4]CS and [Leu5]CS.
• TRABER, R.;HOFMANN, H.;HAERRI, E.;KUHN, M.
  作者：TRABER, R.、HOFMANN, H.、HAERRI, E.、KUHN, M.

  DOI：——

  日期：——
• LYOPHILIZATION PROCESS AND PRODUCTS OBTAINED THEREBY
  申请人：Scidose, Llc

  公开号：EP1954244A1

  公开（公告）日：2008-08-13