(1R,3R,5S,8S,9S,12R,13R,14S)-1-hydroxy-14-(2-hydroxypropan-2-yl)-13-methyl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione;(1R,3R,5S,8S,9S,12R,13R,14R)-1-hydroxy-13-methyl-14-prop-1-en-2-yl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione | 124-87-8

• 物质功能分类: 原料药 - 神经系统用药 - 中枢兴奋药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (1R,3R,5S,8S,9S,12R,13R,14S)-1-hydroxy-14-(2-hydroxypropan-2-yl)-13-methyl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione;(1R,3R,5S,8S,9S,12R,13R,14R)-1-hydroxy-13-methyl-14-prop-1-en-2-yl-4,7,10-trioxapentacyclo[6.4.1.19,12.03,5.05,13]tetradecane-6,11-dione
• CAS: 124-87-8
• 化学式: C30H34O13
• 分子量: 602.6
• InChiKey: VJKUPQSHOVKBCO-NGKRNLQBSA-N

物化性质

• 熔点：
  203 °C(lit.)
• 沸点：
  571.75°C (rough estimate)
• 比旋光度：
  D16 -29.3° (c = 4 in abs ethanol)
• 密度：
  1,28 g/cm3
• 溶解度：
  乙醇：50 mg/mL，澄清至轻微混浊
• 物理描述：
  Cocculus appears as a poisonous berry, the dried fruit of Anamirta cocculus L. Contains several substances including about one percent picrotoxin. Pure picrotoxin occurs as shiny leaflets with an intensely bitter taste or as a microcrystalline powder. Very poisonous!. Used in medicine as a central nervous system stimulant and antidote for barbiturate poisoning. Not currently regarded as a useful therapeutic agent.
• 颜色/状态：
  Shiny rhomboid leaflets
• 气味：
  Odorless
• 味道：
  Very bitter
• 稳定性/保质期：
  Stable in air; affected by light
• 旋光度：
  Specific rotation: -29.3 deg @ 16 °C/d (absolute ethanol, c= 4)
• 分解：
  When heated to decomposition it emits acrid smoke and fumes

计算性质

• 辛醇/水分配系数(LogP)：
  -0.93
• 重原子数：
  43
• 可旋转键数：
  2
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  191
• 氢给体数：
  3
• 氢受体数：
  13

ADMET

毒理性

• 人类毒性摘录

一名年轻女性因食用了被毒扁豆碱毒死的鱼而发生了罕见的中毒病例，累及眼睛。她出现了头痛、寒战、流涎和视力丧失，瞳孔扩大且无反应。观察到两个视网膜都有水肿。...患者康复了...

An unusual case of poisoning with eye involvement occurred in a young woman who ate fish that had been killed by picrotoxin. She developed headache, chills, salivation, and loss of vision, with the pupils dilated and unreactive. Both retinas were observed to be edematous. ... The patient recovered ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

没有出现明显的苦毒素效果，直到给予惊厥剂量。所产生的惊厥是阵挛性的，不协调的，其模式类似于戊四唑产生的……使用大剂量的苦毒素可能会导致出现强直-阵挛性发作，其中强直屈曲先于强直伸展。伴随惊厥运动的是流涎、由于血管运动刺激导致的血压升高，以及经常性的呕吐。

No appreciable effect of picrotoxin is seen until convulsive doses are given. The resultant convulsion is clonic and incoordinated, and the pattern resembles that produced by pentylenetetrazol ... With large doses of picrotoxin a tonic-clonic seizure may occur in which tonic flexion precedes tonic extension. Accompanying the convulsive movements are salivation, elevation of blood pressure due to vasomotor stimulation, and frequently emesis.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

Picrotoxin是一种剧毒物质，20毫克的剂量可能会产生严重中毒症状。人类的致死剂量尚不清楚。

Picrotoxin is a highly toxic substance, and a dose of 20 mg may produce symptoms of severe poisoning. The fatal dose for man is unknown.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

猫和兔子的实验表明，根据毒扁豆碱的剂量，视神经神经元的电活动和视觉诱发皮层反应都有所减少和增强。对青蛙视网膜活性的抑制作用已经得到证实。

Experiments in cats and rabbits have shown both reduction and enhancement of electrical activity of optic nerve neurons and visual evoked cortical responses, depending on the dosage of picrotoxin. Inhibitory effect on frog retina activity has been shown.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

<Picrotoxin>是对鱼类高度有毒的。

/Picrotoxin is/ highly toxic to fish.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尽管毒扁豆碱可以通过所有途径被吸收，但是对中枢神经系统产生完整效果需要几分钟的时间，即使是通过静脉给药。其作用持续时间相对较短。

Although picrotoxin is absorbed by all routes, the full effect on the central nervous system is not seen for several minutes, even when the drug is admin intravenously. Its duration action is relatively brief.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+,T,N
• 安全说明：
  S28,S36/37/39,S45,S61
• 危险类别码：
  R52/53,R28
• WGK Germany：
  3
• 海关编码：
  29322985
• 危险品运输编号：
  UN 3462 6.1/PG 2

制备方法与用途

类别：有毒物品

• 毒性分级：剧毒
• 急性毒性：
  • 腹注-大鼠 LD50: 1.99 毫克/公斤
  • 口服-小鼠 LD50: 15 毫克/公斤

可燃性危险特性：不易燃

储运特性：库房通风、低温干燥；与食品分开储运

灭火剂：水、泡沫、二氧化碳、砂土

文献信息

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  公开号：US20170267686A1

  公开（公告）日：2017-09-21

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  公开号：WO2015021561A1

  公开（公告）日：2015-02-19

  Methods for the manufacture of the therapeutic chemical compound noscapine and noscapine synthesis intermediates comprising contacting a noscapine pathway precursor selected from a first canadine derivative, a first papaveroxine derivative and narcotine hemiacetal with at least one of the enzymes selected from the group CYP82Y1, CYP82X1, AT1, CYP82X2, OMT, CXE1 and NOS.

  制备治疗化合物诺斯卡平和诺斯卡平合成中间体的方法包括将选自第一类肉桂碱衍生物、第一类罂粟碱衍生物和纳科汀半缩醛的诺斯卡平途径前体与来自CYP82Y1、CYP82X1、AT1、CYP82X2、OMT、CXE1和NOS组中至少一种酶中的至少一种接触。
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  申请人：River Stone Biotech APS

  公开号：US20210230655A1

  公开（公告）日：2021-07-29

  The invention relates to recombinant host cells that expresses one or more genes encoding a cytochrome P450 enzyme capable of N-demethylating and/O-demethylating reticuline and/or derivatives thereof, and also methods of producing a N-demethylated and/or O-demethylated reticuline and/or derivatives thereof, comprising cultivating the recombinant host of the invention in a culture medium under conditions in which the one or more genes encoding the cytochrome P450 enzymes is/are expressed. The reticuline and derivatives thereof are useful for providing access to naturally unavailable and chemically difficult-to-produce starting materials for opioids.

  该发明涉及重组宿主细胞，该细胞表达一个或多个编码细胞色素P450酶的基因，该酶能够对莱角碱和/或其衍生物进行N-去甲基化和/或O-去甲基化，并且还涉及生产N-去甲基化和/或O-去甲基化的莱角碱和/或其衍生物的方法，包括在培养基中培养该发明的重组宿主细胞，在该条件下，编码细胞色素P450酶的一个或多个基因被表达。莱角碱及其衍生物可用于提供自然无法获得和化学上难以生产的阿片类药物的起始物质。
• SALT DERIVATIVE OF TETRAHYDROISOQUINOLINE AND CRYSTALLINE THEREOF AND PREPARATION METHOD THEREFORE AND APPLICATION THEREOF
  申请人：CHINA STATE INSTITUTE OF PHARMACEUTICAL INDUSTRY

  公开号：US20190177277A1

  公开（公告）日：2019-06-13

  The present invention discloses a salt derivative of 1-(3-methanesulfonamidobenzyl)-6-methoxy-7-benzyloxy-1,2,3,4-tetrahydroisoquinoline. The salt derivative has a solubility in water of not less than 3.0 nmol/mL or 1.8 mg/mL. The salt derivative has a solubility in water of not less than 3.0 nmol/mL or 1.8 mg/mL.

  本发明公开了1-(3-甲磺胺基苄基)-6-甲氧基-7-苄氧基-1,2,3,4-四氢异喹啉的盐衍生物。该盐衍生物在水中的溶解度不低于3.0 nmol/mL或1.8 mg/mL。
• INHIBITORS OF RNA-GUIDED NUCLEASE TARGET BINDING AND USES THEREOF
  申请人：THE BROAD INSTITUTE, INC.

  公开号：US20210177832A1

  公开（公告）日：2021-06-17

  Compositions and methods for inhibiting the activity of RNA-guided endonucleases, and methods for identifying such compositions are included. Methods of treatment using the inhibitory compounds, formulations and methods are also detailed, as well as control of nucleic acid editing systems and methods using said compounds.

  本发明涉及抑制RNA引导内切酶活性的组合物和方法，以及识别此类组合物的方法。本发明还详细描述了使用抑制剂化合物的治疗方法、制剂和方法，以及使用该化合物控制核酸编辑系统和方法。