Cyclochlorotine | 12663-46-6

• 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: Cyclochlorotine
• 英文别名: (3S,7R,10S,13S,16R,17S,18R)-17,18-dichloro-13-ethyl-3,10-bis(hydroxymethyl)-7-phenyl-1,4,8,11,14-pentazabicyclo[14.3.0]nonadecane-2,5,9,12,15-pentone
• CAS: 12663-46-6
• 化学式: C₂₄H₃₁Cl₂N₅O₇
• 分子量: 572.445
• InChiKey: PMBVHCCVEPYDSN-BADCMNFISA-N

物化性质

• 熔点：
  255°C
• 沸点：
  249°C (rough estimate)
• 密度：
  1.5344 (rough estimate)
• 颜色/状态：
  WHITE NEEDLES FROM METHANOL
• 溶解度：
  SOL IN WATER & N-BUTANOL
• 旋光度：
  SPECIFIC OPTICAL ROTATION (ETHANOL): -92.9 DEG @ 16 °C/D; MAX ABSORPTION: 257 NM (LOG E= 9.81)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  177
• 氢给体数：
  6
• 氢受体数：
  7

ADMET

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据不足。总体评估：第3组：该物质对人类致癌性无法分类。

No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：环氯素

IARC Carcinogenic Agent:Cyclochlorotine

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：对其对人类的致癌性无法分类

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第10卷：（1976年）一些天然存在的物质

IARC Monographs:Volume 10: (1976) Some Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 相互作用

微生物毒素环氯菌素（0.8毫克/千克，IP，每周5天）连续50次给予小鼠，导致电镜下观察到肝脏亚包膜区域和肝小叶周围的纤维化。在门脉周围纤维化发展之前，观察到周围小叶细胞损伤和门脉周围塌陷。当实验动物在整个实验期间同时喂食含有0.5%苯巴比妥的饮食时，与对照相比，亚包膜区域的纤维化增强。在环氯菌素治疗停止后，纤维化的程度有所减少。

THE MICROBIAL TOXIN CYCLOCHLOROTINE (0.8 MG/KG, IP, 5 DAYS/WEEK) ADMINISTERED TO MICE 50 TIMES CAUSED LIVER FIBROSIS IN THE SUBCAPSULAR REGION AND THE PERIPHERY OF LIVER LOBULES AS DEMONSTRATED BY ELECTRON MICROSCOPY. THE PERILOBULAR CELL DAMAGE AND PERIPORTAL COLLAPSE WERE OBSERVED PRIOR TO DEVELOPMENT OF THE PERIPORTAL FIBROSIS. WHEN THE EXPERIMENTAL ANIMALS WERE CONCOMITANTLY FED A DIET CONTAINING 0.5% PHENOBARBITAL THROUGHOUT THE ENTIRE EXPERIMENTAL PERIOD, FIBROSIS IN THE SUBCAPSULAR REGION WAS ENHANCED COMPARED TO CONTROLS. AFTER CESSATION OF CYCLOCHLOROTINE TREATMENT, THE DEGREE OF FIBROSIS WAS REDUCED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服放射性氚标记的环氯硝唑在动物体内迅速出现在肝脏中，剂量的73%通过尿液排出。

ORALLY ADMIN TRITIUM-LABELED CYCLOCHLOROTINE APPEARED RAPIDLY IN THE LIVER /OF ANIMALS/, & 73% OF THE DOSE WAS EXCRETED IN THE URINE.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

类别：有毒物质
毒性分级：剧毒
急性毒性：口服-大鼠 LD50: 5 毫克/公斤；口服-小鼠 LD50: 6.55 毫克/公斤
可燃性危险特性：可燃，燃烧时分解出有毒的氯化物和氮氧化物气体
储运特性：库房应保持低温、通风干燥，并与食品原料分开存放
灭火剂：水、二氧化碳、干粉、砂土

文献信息

• [EN] MACROCYCLIZATION OF PEPTIDOMIMETICS<br/>[FR] MACROCYCLISATION DE PEPTIDOMIMÉTIQUES
  申请人：UNIV WARWICK

  公开号：WO2019186174A1

  公开（公告）日：2019-10-03

  The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.

  该发明提供了一种改进的肽类类似物的大环化方法，通过孤立产量和产物分布来衡量，其中包括用诱导转向基团替代一个或多个骨架酰胺C=O键。该方法是通用的，在一系列环大小（例如三肽、四肽、五肽和六肽）中均可见到增强效果。具体而言，该发明提供了一种包含具有结构的羰基生物等同体诱导转向元素的肽类类似物大环：（I）其中X是杂原子；其中R1至R6分别独立地选自烷基、芳基、杂芳基和氢。
• Compositions and methods for improving integrity of compromised body passageways and cavities
  申请人：ANGIOTECH INTERNATIONAL AG

  公开号：EP1568363A2

  公开（公告）日：2005-08-31

  The present invention provides compositions and methods for improving the integrity of body passageways following surgery or injury. Representative examples of therapeutic agents include microtubal stabilising agents, fibrosis inducers, angiogenic factors, growth factors and cytokines and other factors involved in the wound healing or fibrosis cascade.

  本发明提供了用于改善手术或损伤后体内通道完整性的组合物和方法。治疗剂的代表性实例包括微管稳定剂、纤维化诱导剂、血管生成因子、生长因子和细胞因子以及参与伤口愈合或纤维化级联的其他因子。
• Composition and methods for immproving integrity of compromised body passageways and cavities
  申请人：——

  公开号：US20020022055A1

  公开（公告）日：2002-02-21

  The present invention provides compositions and methods for improving the integrity of body passageways following surgery or injury. Representative examples of therapeutic agents include microtubule stabilizing agents, fibrosis inducers, angiogenic factors, growth factors and cytokines and other factors involved in the wound healing or fibrosis cascade.

  本发明提供了用于改善手术或损伤后体内通道完整性的组合物和方法。治疗剂的代表性实例包括微管稳定剂、纤维化诱导剂、血管生成因子、生长因子和细胞因子以及参与伤口愈合或纤维化级联的其他因子。
• COMPOSITIONS AND METHODS FOR IMPROVING INTEGRITY OF COMPROMISED BODY PASSAGEWAYS AND CAVITIES
  申请人：ANGIOTECH INTERNATIONAL AG

  公开号：EP1162956B1

  公开（公告）日：2005-06-08
• PRODUCTION OF MONASCUS-LIKE AZAPHILONE PIGMENT
  申请人：DTU, Technical University Of Denmark

  公开号：EP2262862A2

  公开（公告）日：2010-12-22