氟鼠灵 | 90035-08-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 氟鼠灵
• 中文别名: 4-羟基-3-{1,2,3,4-四氢-3-[4-(4-三氟甲基苄氧基)苯基]-1-萘基}香豆素；氟鼠酮；氟羟香豆素；杀它仗；3-[3-(4'-三氟甲基苄基氧代苯-4-基)-1,2,3,4-四氢-1-萘基]-4-羟基香豆素
• 英文名称: flocoumafen
• 英文别名: 1R-(4-hydroxycoumarin-3-yl)-3R-[4-(4-trifluoromethylbenzyloxy)phenyl]-1,2,3,4-tetrahydronaphthalene；4-hydroxy-3-[3-[4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]-1,2,3,4-tetrahydronaphthalen-1-yl]chromen-2-one
• CAS: 90035-08-8
• 化学式: C₃₃H₂₅F₃O₄
• 分子量: 542.554
• InChiKey: KKBGNYHHEIAGOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

代谢

在flocoumafen管理员之后，大鼠肝脏残留物主要由未改变的flocoumafen组成，尽管在重复剂量研究中检测到了一个极性代谢物。在经皮暴露于14C-flocoumafen后，检测到了8种尿液代谢物。

Following admin of flocoumafen, liver residues in rats consisted mainly of unchanged flocoumafen, although in a repeat dose study a polar metabolite was detected. Eight urinary metabolites were detected after percutaneous exposure to 14C-flocoumafen.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在雄性日本鹌鹑中进行的研究表明，口服14C-flocoumafen后，其代谢和消除速度比大鼠要快。在排泄物中检测到了多达12种放射性成分。

Studies in male Japanese quail have shown more rapid metabolism and elimination than in the rat following an oral dose of 14C-flocoumafen. Up to 12 radioactive components were detected in the excreta.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠（静脉注射）和日本鹌鹑（口服，腹腔注射）中，福氯马芬被代谢为多种羟基香豆素。

In rats (iv) and Japanese quail (oral, ip), flocoumafen is metabolised to a number of hydroxycoumarins.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在 0.02 和 0.1 毫克/千克/周的剂量下给大鼠口服多次...flocoumafen 并没有广泛代谢...在高剂量下...2个极性代谢物和一个亲脂性化合物是粪便中的次要产物。随着累积剂量的增加，极性产物的量也随之增加。

Following multiple oral admin ...to rats at 0.02 and 0.1 mg/kg/wk, ...flocoumafen was not extensively metabolized... . At the high dose, ...2 ...polar metabolites and a lipophilic compound were minor products in feces. Amounts of the polar products increased with cumulative dosage received. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

这种物质可以通过吸入、皮肤接触和摄入被身体吸收。

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

来源:ILO International Chemical Safety Cards (ICSC)

毒理性

• 吸入症状

见摄取。

See Ingestion.

来源:ILO International Chemical Safety Cards (ICSC)

毒理性

• 皮肤症状

可能被吸收！请参阅摄入部分。

MAY BE ABSORBED! See Ingestion.

来源:ILO International Chemical Safety Cards (ICSC)

毒理性

• 摄入症状

症状可能会延迟。多处自发出血。

Symptoms may be delayed. Spontaneous bleeding from various sites.

来源:ILO International Chemical Safety Cards (ICSC)

毒理性

• 相互作用

以下药物可能会增加对香豆素或香豆素衍生物的反应：酒精（急性中毒）、别嘌醇、氨基水杨酸、胺碘酮、雄激素类固醇、水合氯醛、氯霉素、西咪替丁、氯贝特、复方新诺明、达那唑、碘噻吨钠、二氮嗪、二氟尼柳、双硫仑、红霉素、依他尼酸、非诺洛芬钙、胰高血糖素、布洛芬、吲哚美辛、流感病毒疫苗、异烟肼、美洛昔康、甲芬那酸、甲巯咪唑、甲硝唑、咪康唑、萘啶酸、新霉素（口服）、己酮可可碱、保泰松、丙氧酚、丙硫氧嘧啶、奎尼丁、奎宁、水杨酸盐、链激酶、磺吡酮、磺胺类药物、舒林酸、四环素、噻嗪类利尿剂、甲状腺药物、三环类抗抑郁药、尿激酶、维生素E。/香豆素和香豆素衍生物/

The following drugs ... may increase ... response to coumarin or indandione derivatives: alcohol (acute intoxication), allopurinol, aminosalicylic acid, amiodarone, anabolic steroids, chloral hydrate, chloramphenicol, cimetidine, clofibrate, co-trimoxazole, danazol, dextrothyroxine sodium, diazoxide, diflunisal, disulfiram, erythromycin, ethacrynic acid, fenoprofen calcium, glucagon, ibuprofen, indomethacin, influenza virus vaccine, isoniazid, meclofenamate, mefenamic acid, methylthiouracil, metronidazole, miconazole, nalidixic acid, neomycin (oral), pentoxifylline, phenylbutazone, propoxyphene, propylthiouracil, quinidine, quinine, salicylates, streptokinase, sulfinpyrazone, sulfonamides, sulindac, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, vitamin E. /Coumarin & indandione derivatives/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠单次口服14C-flocoumafen（0.14 mg/kg体重）后，药物迅速吸收进入血液，在4小时内达到血浆中的最高浓度（0.03-0.05微克/毫升）......粪便排泄......在7天期间占给药量的23-26%；大约一半在最初的24小时内回收。在7天内，少于0.5%的给药量出现在尿液中......发现身体保留程度很高......（给药量的74-76%）；大约一半的给药量在肝脏中找到。

After a single oral dose of 14C-flocoumafen (0.14 mg/kg bw) to rats, the absorption into blood was rapid, reaching max concns (0.03-0.05 ug/ml) in plasma within 4 hr. ...Fecal elimination ... accounted for 23-26% of the dose over the 7-day period; approx half of this was recovered within the first 24 hr. Less than 0.5% of the dose appeared in the urine within 7 days. ...A high degree of body retention was found ...(74-76% of the administered dose); approximately half the dose was found in the liver.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给大鼠每周一次口服14C-flocoumafen剂量为0.02毫克/千克体重或0.1毫克/千克体重，持续最多14周后，大约有1/3的每周低剂量在3天内通过粪便排出，大部分在最初的24小时内排出。在高剂量下，第一次给药后的排出率从18%增加到第十次给药后的59%。...在肝脏中观察到了明显的积累。在两个剂量水平上，组织中浓度最高的是肝脏，其次是肾脏>皮肤>肌肉>脂肪>血液。低剂量组在肝脏中的残留量从一周后的0.1毫克/千克组织增加到第14周的2.1毫克/千克。

After oral 14C-flocoumafen doses of 0.02 mg/kg bw or 0.1 mg/kg bw were given to rats, once weekly for up to 14 weeks, approx 1/3 of each weekly low dose was eliminated through the feces within 3 days, mostly within the first 24 hr. At the higher dose the elimination ranged from 18% after the first dose to 59% after the tenth dose. ...Appreciable accumulation was seen in the liver. At both dose levels tissue concns were highest in the liver, followed by the kidney >skin >muscle >fat >blood. The hepatic residue in the low-dose group ranged from 0.1 mg/kg tissue after one wk to 2.1 mg/kg by wk 14.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

14C-flocoumafen（0.17 mg/kg bw）以较大比例溶解在丙酮中，发现在大鼠尿液中（10%）的比例高于等效口服剂量（<0.5%）的情况，持续7天。粪便排出的比例占经皮剂量的31%。……最大比例……位于肝脏（剂量为25%，浓度为0.8 mg/kg），尽管这比口服剂量低10倍。

A larger proportion of a percutaneous dose of 14C-flocoumafen (0.17 mg/kg bw) dissolved in acetone was found in the urine of rats (10%) than in the case of an equivalent oral dose (<0.5%) over a 7-day period. Fecal elimination accounted for 31% of the percutaneous dose. ...The largest proportion ...was located in the liver (25% of the dose at a concn of 0.8 mg/kg), although this was 10 times lower than that following an oral dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

约8%的给药剂量（0.4毫克/千克）的福尔马酸氟在比格犬肝脏中保留，给药后43周被发现。

...Retention of about 8% of an administered flocoumafen dose of 0.4 mg/kg in the liver of beagle dogs 43 weeks after dosing /was found/.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠连续口服14C-flocoumafen 0.02和0.1 mg/kg/wk后，肝脏中出现了明显的细胞积累。在低剂量下，整个实验期间（14周）肝脏中的残留物随着剂量的增加而增加，但在高剂量下，4周后达到了一个平台期。主要成分是不变的flocoumafen，以及一个在粪便中也可见的微极性代谢物。数据表明，在大鼠肝脏中存在一个可饱和的高亲和力结合位点以及一个低亲和力的第二个结合位点。只有当结合位点饱和时，才会发生致命的抗凝作用。一系列血液学和临床化学测量未能预测高剂量治疗组中出现的抗凝毒性。Flocoumafen没有广泛代谢；在低剂量下，每次给药后3天内约有30%的累积给药剂量以未改变的杀鼠剂形式在粪便中排出。在高剂量下，这个值从第一次给药后的18%变化到第十次给药后的59%。两个更极性的代谢物和一个亲脂性化合物是粪便中的次要产物。随着累积剂量的增加，极性产物的量也在增加。在两种剂量下，尿液排出途径都是一个非常小的途径（<1.6%）。

Following multiple oral admin of 14C-flocoumafen to rats at 0.02 and 0.1 mg/kg/wk, appreciable cellular accumulation was seen in the liver. Residues in the liver increased with dose throughout the duration of the experiment (14 weeks) at the low dose, but reached a plateau after 4 weeks at the high dose. The major component was unchanged flocoumafen together with a minor polar metabolite seen also in feces. The data suggest the presence in rat liver of a saturable high-affinity binding site for flocoumafen and a second binding site of lower affinity. Lethal anticoagulant action occurs only when the binding sites have become saturated. A range of hematological and clinical chemistry measurements failed to predict the onset of anticoagulant toxicity seen in the high dose treatment group. Flocoumafen was not extensively metabolised; at the low dose, approx 30% of the cumulative administered dose was eliminated in the feces within 3 days of each dosing, mainly as unchanged rodenticide. At the high dose, this value ranged from 18% after the first dose to 59% after the tenth dose. Two more polar metabolites and a lipophilic compound were minor products in feces. Amounts of the polar products increased with cumulative dosage received. The urinary route of elimination was a very minor one (<1.6%) at both doses.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开储运。

制备方法与用途

制备方法

3-[(4-(4-三氟甲基苄氧基)苯基]-1,2,3,4-四氢-1-萘酚的制备：将4-三氟甲基溴苄与萘满酮在DMF中于室温反应，产物再用NaBH₄还原得到目标化合物。

合成制备方法

同样地，3-[(4-(4-三氟甲基苄氧基)苯基]-1,2,3,4-四氢-1-萘酚的制备步骤为：将4-三氟甲基溴苄与萘满酮在DMF中于室温反应，产物再用NaBH₄还原得到目标化合物。

用途简介

该化合物是一种第二代抗凝血剂，具有强毒力、良好的适口性和显著的灭鼠效果。它可用于防治家栖和野栖鼠类以及对其他杀鼠剂产生抗性的鼠种。然而，由于氟鼠酮高毒，请在使用时注意安全。

用途

该化合物是第二代抗凝血剂，具有强毒力、良好的适口性和显著的灭鼠效果，可用于防治家栖和野栖鼠类以及对其他杀鼠剂产生抗性的鼠种。需要注意的是，氟鼠酮高毒，在使用过程中务必注意安全。

反应信息

• 作为反应物：
  描述：

  氟鼠灵 生成 2H-1-Benzopyran-2-one, 4-hydroxy-3-(1,2,3,4-tetrahydro-3-(4-((4-(trifluoromethyl)phenyl)methoxy)phenyl)-1-naphthalenyl)-, trans-
  参考文献：
  名称：

  SWAINE, H.

  摘要：

  DOI：
• 作为产物：
  描述：

  3-(4-hydroxyphenyl)-3,4-dihydronaphthalen-1(2H)-one 在 sodium tetrahydroborate 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 氟鼠灵 、 trans-4-hydroxy-3-[1,2,3,4-tetrahydro-3-[4-(4-trifluoromethylbenzyloxy)phenyl]-1-naphthyl]coumarin
  参考文献：
  名称：

  氟古马芬及其结构异构体的简单合成及生物学评价

  摘要：

  描述了氟考马芬1及其结构异构体的简单合成及其生物学特性。关键的合成策略包括Knoevenagel缩合，Grignard反应，分子内环环化和偶联反应。使用快速柱色谱法可轻松将Flocoumafen 1分离为顺式和反式形式。然后评估它们在体外对LPS诱导的NO生成的抑制作用和抗兴奋性毒性。发现反式氟尿嘧啶在体外浓度为10 µM时可有效抑制NO生成，而对培养的皮层神经元的神经毒性无明显影响。

  DOI：

  10.1007/s12039-010-0071-2

文献信息

• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• Novel insecticides
  申请人：Syngenta Participations AG

  公开号：EP2540718A1

  公开（公告）日：2013-01-02

  Compounds of formula I wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts and all stereoisomers and tautomeric forms of the compounds of formula I can be used as insecticides and can be prepared in a manner known per se.

  式I的化合物 其中取代基如权利要求1所定义，并且式I化合物的农药可接受盐以及所有立体异构体和互变异构形式可用作杀虫剂，并且可以按照已知的方法制备。
• Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
  申请人：Dow AgroSciences LLC

  公开号：US20180279612A1

  公开（公告）日：2018-10-04

  This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

  这份披露涉及具有对节肢动物门、软体动物门和线虫门害虫具有杀虫效用的分子领域，用于生产此类分子的过程，用于此类过程的中间体，含有此类分子的杀虫组合物，以及使用此类杀虫组合物对抗此类害虫的过程。这些杀虫组合物可以用作螨虫剂、杀虫剂、螨虫剂、软体动物杀虫剂和线虫杀虫剂。本文件披露了具有以下式（“式一”）的分子。
• [EN] MOLECULES HAVING PESTICIDAL UTILITY, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES, RELATED THERETO<br/>[FR] MOLÉCULES PRÉSENTANT UNE UTILITÉ EN TANT QUE PESTICIDE, ET LEURS INTERMÉDIAIRES, COMPOSITIONS ET PROCÉDÉS
  申请人：DOW AGROSCIENCES LLC

  公开号：WO2017040194A1

  公开（公告）日：2017-03-09

  This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions aga inst such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula ("Formula One").

  这份披露涉及具有对节肢动物门、软体动物门和线虫门害虫有用的分子领域，用于生产这种分子的过程，用于这种过程的中间体，含有这种分子的杀虫剂组合物，以及使用这种杀虫剂组合物对抗这些害虫的过程。这些杀虫剂组合物可以用作螨虫剂、杀虫剂、螨虫剂、软体动物杀虫剂和线虫杀虫剂。本文件披露了具有以下化学式（“化学式一”）的分子。