(5-benzylfuran-3-yl)methyl (1R,3S)-2,2-dimethyl-3-[(Z)-(2-oxothiolan-3-ylidene)methyl]cyclopropane-1-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5-benzylfuran-3-yl)methyl (1R,3S)-2,2-dimethyl-3-[(Z)-(2-oxothiolan-3-ylidene)methyl]cyclopropane-1-carboxylate
• 化学式: C₂₃H₂₄O₄S
• 分子量: 396.5
• InChiKey: UGWALRUNBSBTGI-JXOUBNESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  81.8
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

在大鼠中，口服给药后，会发生快速的代谢（通过打开硫内酯环、酯键断裂和环羟基化）。

In rats, following oral administration, there is rapid metabolism (by opening of the thiolactone ring, cleavage of the ester, and ring hydroxylation)... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

拟除虫菊酯类化合物的代谢途径在不同哺乳动物物种之间变化不大，但与结构有一定的关系。基本上，除虫菊和驱蚊剂（allethrin）主要通过氧化酸部分中的异丁烯基侧链和醇部分中的不饱和侧链，以及酯水解来分解，而对于其他拟除虫菊酯类化合物，酯水解占主导地位。

The metabolic pathways for the breakdown of the pyrethroids vary little between mammalian species but vary somewhat with structure. ... Essentially, pyrethrum & allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid moiety & of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing an important part, whereas for the other pyrethroids ester hydrolysis predominates. /Pyrethrum and pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)

代谢

哺乳动物对拟除虫菊酯的相对抗性几乎完全归因于它们能够迅速将拟除虫菊酯水解为其不活性的酸和醇成分，因为直接注射到哺乳动物的中央神经系统会导致与昆虫中观察到的相似易感性。恒温生物的一些额外抗性也可以归因于拟除虫菊酯的作用负温度系数，这意味着在哺乳动物体温下毒性较低，但主要效果是代谢性的。拟除虫菊酯的代谢消除非常迅速，这意味着通过静脉注射的毒性很高，通过较慢的口服吸收毒性适中，而通过皮肤吸收的毒性通常很低。/拟除虫菊酯/

The relative resistance of mammals to the pyrethroids is almost wholly attributable to their ability to hydrolyze the pyrethroids rapidly to their inactive acid & alcohol components, since direct injection into the mammalian CNS leads to a susceptibility similar to that seen in insects. Some additional resistance of homeothermic organisms can also be attributed to the negative temperature coefficient of action of the pyrethroids, which are thus less toxic at mammalian body temperatures, but the major effect is metabolic. Metabolic disposal of the pyrethroids is very rapid, which means that toxicity is high by the iv route, moderate by slower oral absorption, & often unmeasureably low by dermal absorption. /Pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)

代谢

最快的水解和氧化攻击发生在具有反式取代酸的初级醇酯上。对于所有次级醇酯和初级醇顺式取代环丙烷甲酸酯，氧化攻击是主要的。/拟除虫菊酯/

FASTEST BREAKDOWN IS SEEN WITH PRIMARY ALCOHOL ESTERS OF TRANS-SUBSTITUTED ACIDS SINCE THEY UNDERGO RAPID HYDROLYTIC & OXIDATIVE ATTACK. FOR ALL SECONDARY ALCOHOL ESTERS & FOR PRIMARY ALCOHOL CIS-SUBSTITUTED CYCLOPROPANECARBOXYLATES, OXIDATIVE ATTACK IS PREDOMINANT. /PYRETHROIDS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

拟除虫菊酯类物质的解毒...在苍蝇中很重要，可能由于添加了增效剂...如有机磷或氨基甲酸酯...来保证致死效果而延迟。

/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ... /Pyrethroid/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

胡椒基丁醚通过抑制负责在节肢动物中代谢除虫菊酯的水解酶，从而增强除虫菊酯的杀虫活性。当胡椒基丁醚与除虫菊酯结合使用时，后者的杀虫活性可增加2-12倍。

Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在1000 ppm杀虫剂和10000 ppm氧化胡椒基丁的饮食水平下...在大鼠肝细胞中的增大、边缘化和细胞质包涵体...仅在8天内就得到了很好的发展，但是...并没有达到最大。变化与剂量成正比，并且与DDT产生的变化相似。这两种物质的效果是累加的。/杀虫剂/

At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

添加剂（例如石油馏分），如果存在，对患者造成的毒性威胁大于活性成分本身。 ... 当存在石油馏分添加剂时，不应诱导呕吐。 ... 在没有其他有毒成分的情况下，意识清醒且咽喉反射正常的人摄入亚致死剂量的除虫菊酯后，可以通过服用吐根糖浆诱导呕吐，随后使用盐水泻药和活性炭悬浮液。 ... 肺部和过敏后遗症对症治疗，包括维持呼吸道通畅、吸氧和必要时提供呼吸支持。治疗支气管痉挛和过敏性休克的常规药物和管理方案可以使用。癫痫发作可以用地西泮治疗。 /除虫菊酯和合成拟除虫菊酯/

The additives (e.g. petroleum distillate), when present, represent a greater toxic threat to the patient than the active ingredient itself. ... Emesis should not be induced when petroleum distillate additives are present. ... The alert person with an intact gag reflex & a sublethal pyrethrum ingestion without other toxic constituents may have emesis induced by ipecac, followed by a saline cathartic & slurry of activated charcoal. ... Pulmonary & allergic sequelae are treated symptomatically with airway maintenance, oxygen, & ventilatory assistance as required. Standard drugs and management protocols may be used for treatment of bronchospasm & anaphylaxis. Seizures are treated with diazepam. /Pyrethrum and synthetic pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

皮肤去污。立即用肥皂和水清洗皮肤...。如果出现刺激或感觉异常效应，应通过医生获得治疗。由于拟除虫菊酯的挥发显然是导致面部感觉异常的原因，应采取强烈措施（通风、保护面罩和头罩）以避免蒸汽接触面部和眼睛。维生素E油制剂（dL-α-生育酚醋酸酯）在预防和停止感觉异常反应方面具有独特效果。它们适用于现场条件下的皮肤应用。玉米油也有一定效果，但可能的副作用使得长期使用不太合适。凡士林的效果不如玉米油。氧化锌实际上会加剧反应。/拟除虫菊酯/

Skin decontamination. Wash skin promptly with soap and water ... . If irritant or paresthetic effects occur, obtain treatment by a physician. Because volatilization of pyrethroids apparently accounts for paresthesia affecting the face, strenuous measures should be taken (ventilation, protective face mask and hood) to avoid vapor contact with the face and eyes. Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely effective in preventing and stopping the paresthetic reaction. They are safe for application to the skin under field conditions. Corn oil is somewhat effective, but possible side effects with continuing use make it less suitable. Vaseline is less effective than corn oil. Zinc oxide actually worsens the reaction. /Pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中，口服给药后，存在……快速排泄。

In rats, following oral administration, there is ... rapid excretion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/PYRETHROIDS/迅速渗透昆虫外皮，正如通过在美洲大蠊（蟑螂）体表施用的LD50所显示的... /PYRETHROIDS/

/PYRETHROIDS/ READILY PENETRATE INSECT CUTICLE AS SHOWN BY TOPICAL LD50 TO PERIPLANETA (COCKROACH) ... /PYRETHROIDS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当放射性拟除虫菊酯通过口服给哺乳动物时，它会被动物的小肠吸收并在检查的每个组织中分布。在给大鼠口服顺式异构体的情况下：剂量为500毫克/千克；间隔20天；尿液中有36%的放射性排出，粪便中有64%，总共为100%。/拟除虫菊酯/

WHEN RADIOACTIVE PYRETHROID IS ADMIN ORALLY TO MAMMALS, IT IS ABSORBED FROM INTESTINAL TRACT OF THE ANIMALS & DISTRIBUTED IN EVERY TISSUE EXAMINED. EXCRETION OF RADIOACTIVITY IN RATS ADMIN TRANS-ISOMER: DOSAGE: 500 MG/KG; INTERVAL 20 DAYS; URINE 36%; FECES 64%; TOTAL 100%. /PYRETHROIDS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

拟除虫菊酯通过完整皮肤局部应用时可以被吸收。当动物接触到含有胡椒基丁氧基的拟除虫菊酯气溶胶时，这种混合物几乎没有或没有系统性吸收。/拟除虫菊酯/

Pyrethrins are absorbed through intact skin when applied topically. When animals were exposed to aerosols of pyrethrins with piperonyl butoxide being released into the air, little or none of the combination was systemically absorbed. /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尽管一些拟除虫菊酯类化合物的低毒性可能归因于有限的吸收，但通过哺乳动物肝脏酶（酯水解和氧化）的快速生物降解可能是主要负责因素。大多数拟除虫菊酯代谢物会迅速被肾脏部分排出。/拟除虫菊酯/

Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney. /Pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)