lasiocarpine | 303-34-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: lasiocarpine
• 英文别名: [(7S,8R)-7-[(Z)-2-methylbut-2-enoyl]oxy-5,6,7,8-tetrahydro-3H-pyrrolizin-1-yl]methyl (2R)-2,3-dihydroxy-2-[(1S)-1-methoxyethyl]-3-methylbutanoate
• CAS: 303-34-4
• 化学式: C₂₁H₃₃NO₇
• 分子量: 411.496
• InChiKey: QHOZSLCIKHUPSU-LPLKQDONSA-N

物化性质

• 熔点：
  96.5-97.0℃
• 比旋光度：
  D -4° (10% alc)
• 沸点：
  531.2°C (rough estimate)
• 密度：
  1.21±0.1 g/cm3 (20 ºC 760 Torr)
• LogP：
  1.280
• 物理描述：
  Lasiocarpine appears as colorless plates or beige crystalline solid. (NTP, 1992)
• 颜色/状态：
  COLORLESS PLATES
• 溶解度：
  less than 0.1 mg/mL at 68° F (NTP, 1992)
• 稳定性/保质期：
  DECOMP SLOWLY ON STANDING IN AIR @ ROOM TEMP
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -3.0 DEG @ 16 °C/D (IN ETHANOL)
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  8

ADMET

代谢

对LASIOCARPINE的研究已经证实了混合功能氧化酶系统的大鼠肝微粒体部分形成了吡咯代谢物。去氢毛茛碱已被分离和鉴定为LASIOCARPINE的微粒体氧化的产物。

STUDIES WITH LASIOCARPINE HAVE CONFIRMED THE FORMATION OF PYRROLIC METABOLITES BY THE MIXED-FUNCTION OXIDASE SYSTEM OF THE MICROSOMAL FRACTION OF RAT LIVER. DEHYDROHELIOTRIDINE HAS BEEN ISOLATED & IDENTIFIED AS A PRODUCT OF MICROSOMAL OXIDATION OF LASIOCARPINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在尿液中...注射后16小时获得...对大鼠...未改变的毛果芸香碱（剂量的1-1.5%），海葵啶（1.5-3%），海葵啶N-氧化物（6%）和具有欧普因和7-天使海葵啶（预期部分水解产物）色谱性质的碱基痕迹。...24小时尿液样本中的代谢物...给药毛果芸香碱的8.5%。

IN URINE ... OBTAINED 16 HR AFTER INJECTION ... TO RATS ... UNCHANGED LASIOCARPINE (1-1.5% OF DOSE), HELIOTRIDINE (1.5-3%), HELIOTRIDINE N-OXIDE (6%) & TRACES OF BASES WITH CHROMATOGRAPHIC PROPERTIES OF EUROPINE & 7-ANGELYHELIOTRIDINE (EXPECTED PRODUCTS OF PARTIAL HYDROLYSIS). ... METABOLITES IN 24-HR URINE SAMPLE ... 8.5% OF ADMIN LASIOCARPINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类胚胎肝脏切片将吡咯里西啶生物碱LASIOCARPINE转化为吡咯，这通过正艾尔利希显色反应得到指示，而肺组织则没有。

HUMAN EMBRYONIC LIVER SLICES CONVERTED THE PYRROLIZIDINE ALKALOID LASIOCARPINE INTO PYRROLES, AS INDICATED BY A POS EHRLICH COLOR REACTION, WHEREAS LUNG TISSUE DID NOT.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

致癌性分类：1）人类证据：不可用；2）动物证据：充分。对人类致癌风险的总体评估为2B组：该物质可能对人类致癌。/来自表格/

Classification of carcinogenicity: 1) evidence in humans: not available; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans. /From table/

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：鹰靛蓝

IARC Carcinogenic Agent:Lasiocarpine

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：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic 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

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

LASROCARPINE（随机标记，44%在氨基醇中）通过静脉给药给大鼠（总剂量为5毫克），4小时后标记分布如下：胴体，6.4%；肠道，8.6%；睾丸，0.1%；肺，0.05%；肾脏，0.26%；心脏，0.05%；脾，0.01%；大脑，0.03%；尿液，27.2%；肝脏，2.8%，呼出的二氧化碳，9.3% 肝部分馏得到1.73%在三氯乙酸提取物中，0.6%在蛋白质中，0.48%在脂质中，0.005%在核酸中。

LASROCARPINE (RANDOMLY LABELLED, 44% IN THE AMINO ALCOHOL) WAS ADMIN IP TO RATS (TOTAL DOSE, 5 MG) DISTRIBUTION OF LABEL AFTER 4 HR WAS AS FOLLOWS: CARCASS, 6.4%; INTESTINES, 8.6%; TESTES, 0.1%; LUNG, 0.05%; KIDNEY, 0.26%; HEART, 0.05%; SPLEEN, 0.01%; BRAIN, 0.03%; URINE, 27.2%; LIVER, 2.8%, EXPIRED CO2, 9.3% FRACTIONATION OF LIVER RESULTED IN 1.73% IN A TRICHLOROACETIC ACID EXTRACT, 0.6% IN PROTEIN, 0.48% IN LIPID & 0.005% IN NUCLEIC ACIDS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险类别：
  6.1(b)
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  lasiocarpine 在 双氧水 作用下， 生成 lasiocarpine N-oxide
  参考文献：
  名称：

  特征离子簇是使用HPLC-MS分析鉴定含吡咯烷核生物碱的天然产物中吡咯烷核生物碱N-氧化物的决定因素。

  摘要：

  含吡咯烷核生物碱（PA）的植物在世界范围内分布广泛。PA具有肝毒性，影响牲畜和人类。PA N氧化物通常与PA一起存在于植物中，还具有肝毒性，但效力较低。HPLC-MS通常用于分析含PA的草药，尽管在大多数情况下不提供PA参考。但是，迄今为止，没有参考标准，HPLC-MS方法无法将PA N-氧化物与PA区别开来，因为它们在质谱图中都会产生相同的特征离子。在本研究中，使用HPLC-MS系统研究了10种PA N-氧化物和相应PA的质谱，以定义对PAs和PA N-氧化物特有的特征质量碎片离子。有毒逆转录酶型PA N氧化物的质谱在m / z 118-120和136-138处显示两个特征性离子簇。这些离子簇是通过PA N-氧化物的三个独特的断裂途径产生的，并且在其相应的PA中未发现。类似地，无毒的platynecine型PA N氧化物也通过三种相似的途径断裂，从而在m / z 120-122和138-

  DOI：

  10.1002/jms.2969

文献信息

• MANUFACTURE, METHOD AND USE OF ACTIVE SUBSTANCE-RELEASING MEDICAL PRODUCTS FOR PERMANENTLY KEEPING BLOOD VESSELS OPEN
  申请人：Hoffmann Erika

  公开号：US20100063585A1

  公开（公告）日：2010-03-11

  The invention relates to stents and catheter balloons having optimized coatings for eluting rapamycin as well as methods for manufacturing these coatings.

  本发明涉及具有优化涂层以释放雷帕霉素的支架和导管球囊，以及制造这些涂层的方法。
• MANUFACTURE, METHOD AND USE OF DRUG-ELUTING MEDICAL DEVICES FOR PERMANENTLY KEEPING BLOOD VESSELS OPEN
  申请人：Hoffmann Erika

  公开号：US20130005758A1

  公开（公告）日：2013-01-03

  The invention relates to stents and catheter balloons having optimized coatings for eluting rapamycin as well as methods for manufacturing these coatings.

  本发明涉及具有经过优化的涂层以释放雷帕霉素的支架和导管球囊，以及制造这些涂层的方法。
• BALLOON CATHETER WITH POLYMERIC BALLOON HAVING A SURFACE MODIFIED BY A PHOTOACTIVATION REACTION AND METHOD OF MAKING
  申请人：D'Onofrio Simone

  公开号：US20140378897A1

  公开（公告）日：2014-12-25

  A balloon catheter, in particular a balloon catheter for angioplasty, the balloon having an inner or outer surface modified by means of a photoactivation reaction.

  一个气球导管，特别是用于血管成形术的气球导管，该气球通过光活化反应改性内部或外部表面。
• METHOD OF PROLIFERATING HUMAN HEPATOCYTES AND METHOD OF OBTAINING HUMAN HEPATOCYTES
  申请人：Japan Science and Technology Agency

  公开号：EP1496110A1

  公开（公告）日：2005-01-12

  Transplanting human hepatocytes into a liver of an immunodeficient hepatopathy mouse, and then feeding the mouse transplanted with the human hepatocytes under such a condition as being protected from the attack by human complement produced by the human hepatocytes thereby proliferating the transplanted human hepatocytes in the mouse liver. Further, Obtaining human hepatocytes in large scale by repeating the above steps using the proliferated human hepatocytes.

  将人肝细胞移植到免疫缺陷性肝炎小鼠的肝脏中，然后在保护小鼠免受人肝细胞产生的人补体攻击的条件下喂养移植了人肝细胞的小鼠，从而使移植的人肝细胞在小鼠肝脏中增殖。进一步，使用增殖的人类肝细胞重复上述步骤，大规模获得人类肝细胞。
• Expandable medical device for the treatment and prevention of cardiovascular diseases
  申请人：Perelson, Ophir

  公开号：EP1913962A1

  公开（公告）日：2008-04-23

  The invention relates to expandable medical devices such as stents, bioresorbable stents or catheter balloons with or without crimped stents comprising the pharmaceutically active agent gemcitabine as pure compound or incorporated into a drug release matrix optionally in combination with other drugs for the treatment of cardiovascular diseases such as arteriosclerosis, atherosclerosis, stenosis or restenosis and methods for the manufacture of these expandable medical devices.

  本发明涉及用于治疗动脉硬化、动脉粥样硬化、血管狭窄或再狭窄等心血管疾病的可膨胀医疗器械，如支架、生物可吸收支架或带或不带卷边支架的导管球囊，其中包含纯化合物形式的药物活性剂吉西他滨，或将其掺入药物释放基质（可选择与其他药物组合使用），以及制造这些可膨胀医疗器械的方法。