2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carboxylic acid
• 化学式: C₆₇H₁₁₁N₁₃O₁₄
• 分子量: 1322.7
• InChiKey: JYEAZWRDYOTZIN-SFIJKNBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  94
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  345
• 氢给体数：
  7
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carboxylic acid 、 水杨酸 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N-甲基吡咯烷酮 为溶剂， 反应 0.5h， 以13%的产率得到2-[2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carbonyl]oxybenzoic acid
  参考文献：
  名称：

  Cyclosporin derivatives

  摘要：

  本发明涉及不穿过细胞膜的新型环孢素衍生物。根据本发明的化合物用于医药，特别是在治疗/诊断急性及慢性炎症疾病、病毒感染、癌症、退行性肌肉疾病、神经退行性疾病以及与钙稳态受损相关的损害。这些新型环孢素衍生物另外不具有免疫抑制作用。

  公开号：

  US09453051B2
• 作为产物：
  描述：

  在 甲醇 、 lithium hydroxide 作用下， 反应 0.3h， 以87%的产率得到2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carboxylic acid
  参考文献：
  名称：

  Cyclosporin derivatives

  摘要：

  本发明涉及不穿过细胞膜的新型环孢素衍生物。根据本发明的化合物用于医药，特别是在治疗/诊断急性及慢性炎症疾病、病毒感染、癌症、退行性肌肉疾病、神经退行性疾病以及与钙稳态受损相关的损害。这些新型环孢素衍生物另外不具有免疫抑制作用。

  公开号：

  US09453051B2

文献信息

• Anti-inflammatory Effects of Extracellular Cyclosporins Are Exclusively Mediated by CD147
  作者：Miroslav Malesevic、Danny Gutknecht、Erik Prell、Claudia Klein、Michael Schumann、Romana A. Nowak、Jan C. Simon、Cordelia Schiene-Fischer、Anja Saalbach

  DOI：10.1021/jm4007577

  日期：2013.9.26

  Leukocyte trafficking and recruitment is a critical process in host immune surveillance and in inflammatory diseases. Extracellular cyclophilins (eCyps) have been identified as a novel class of chemotactic mediators. The impact of eCyp/CD147 interactions for the recruitment of leukocytes during inflammation was analyzed using a structurally simplified cell-impermeable eCyp inhibitor. This compound was highly effective at inhibiting leukocyte migration toward CypA in vitro as well as in the recruitment of leukocytes during inflammation in a mouse model of experimentally induced peritonitis and delayed-type hypersensitivity reaction. By using CD 147-/- mice in combination with the cell-impermeable eCyp inhibitor, we were able to show that the action of eCyps in inflammation is exclusively mediated by interaction with CD 147. Our findings suggest that blocking eCyps may be an effective therapeutic target for reducing inflammatory diseases associated with leukocyte recruitment.
• CYCLOSPORIN-DERIVATE
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2751127B1

  公开（公告）日：2016-07-27
• US9453051B2
  申请人：——

  公开号：US9453051B2

  公开（公告）日：2016-09-27
• [DE] CYCLOSPORIN-DERIVATE<br/>[EN] CYCLOSPORIN DERIVATIVES<br/>[FR] DÉRIVÉS DE CYCLOSPORINE
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2013030208A1

  公开（公告）日：2013-03-07

  Die vorliegende Erfindung betrifft neue nicht-zellgängige Cyclosporin-Derivate. Die erfindungsgemäßen Verbindungen finden Verwendung in der Medizin, insbesondere in der Behandlung/Diagnose von akuten und chronischen endzündlichen Erkrankungen, viralen Infektionen, Krebs, degenerativen Muskelerkrankungen, neurodegenerativen Erkrankungen und Schädigungen, welche mit Beeinträchtigung der Calcium- Homöostase einhergehen. Zudem weisen die neuen Cyclosporinderivate keine immunsuppressive Wirkung auf.
• Cyclosporin derivatives
  申请人：Fischer Gunter

  公开号：US09453051B2

  公开（公告）日：2016-09-27

  The present invention relates to novel cyclosporin derivatives that do not cross the cellular membrane. The compounds according to the invention are used in medicine, more particularly in the treatment/diagnosis of acute and chronic inflammatory diseases, viral infections, cancer, degenerative muscle diseases, neurodegenerative diseases and damage that is associated with calcium homeostasis impairment. The novel cyclosporin derivatives additionally have no immunosuppressive effect.

  本发明涉及不穿过细胞膜的新型环孢素衍生物。根据本发明的化合物用于医药，特别是在治疗/诊断急性及慢性炎症疾病、病毒感染、癌症、退行性肌肉疾病、神经退行性疾病以及与钙稳态受损相关的损害。这些新型环孢素衍生物另外不具有免疫抑制作用。