emamectin | 119791-41-2

• 物质功能分类: 化学农药原药 - 杀虫剂 - 其他杀虫剂
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: emamectin
• 英文别名: (1'R,2R,3S,4'S,6S,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-2-[(2S)-butan-2-yl]-21',24'-dihydroxy-12'-[(2R,4S,5S,6S)-4-methoxy-5-[(2S,4R,5R,6R)-4-methoxy-6-methyl-5-(methylamino)oxan-2-yl]oxy-6-methyloxan-2-yl]oxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
• CAS: 119791-41-2
• 化学式: C₄₉H₇₅NO₁₃
• 分子量: 886.133
• InChiKey: CXEGAUYXQAKHKJ-FYOMLGFFSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷（少许）、氯仿（少许）、甲醇（少许）
• 颜色/状态：
  White to off-white powder
• 熔点：
  141-146 °C /Emamectin benzoate/
• 密度：
  1.20 at 23 °C /Emamectin benzoate/
• 蒸汽压力：
  3.8X10-8 mm Hg at 21 °C /Emamectin benzoate/
• 旋光度：
  Specific optical rotation: -6.9 deg (c = 0.5% in methanol)
• 分解：
  When heated to decomposition it emits toxic vapors of /Nitrogen oxide/.
• 解离常数：
  pKa: 4.18 (acidic, attributed to benzoate counter ion), 8.71 (basic, attributed to emamectin moiety)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  63
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

大西洋鲑鱼（约1.3公斤）在5±1摄氏度的海水罐中饲养，通过饲料以50微克/公斤/天的名义剂量给予[(3)H]依玛菌素B1苯甲酸盐，连续7天。在最后给药后3小时和12小时以及1、3、7、15、30、45、60和90天，从每组10条鱼中收集组织、血液和胆汁。从最后给药前开始，每天从罐中收集粪便，直到最后给药后90天。在给药期间，每日粪便样本的总放射性残留物（TRR）最大为0.25 ppm，且在覆盖给药期的合并粪便中>97%的TRR是依玛菌素B1a。粪便TRR随后迅速下降，到最后给药后1天大约为0.05 ppm。90天给药期间组织平均TRR的范围如下：肾脏，1.4-3 ppm；肝脏，1.0-2.3 ppm；皮肤，0.04-0.09 ppm；肌肉，0.02-0.06 ppm；骨骼，<0.01 ppm。根据给药后间隔合并的肝脏、肾脏、肌肉和皮肤样本的残留物组成为依玛菌素B1a（81-100% TRR）和去甲基依玛菌素B1a（0-17% TRR），在一些肌肉样本中可以看到N-甲酰依玛菌素B1a的微量（<2%）。选作依玛菌素残留监管监测的标志残留物是依玛菌素B1a。使用高效液相色谱-荧光法量化个体皮肤和肌肉样本中的依玛菌素B1a水平，在所有分析的样本中（给药后3小时至30天）均低于85 ppb。

Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with [(3)H]emamectin B1 benzoate in feed at a nominal rate of 50 ug of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 hr and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 hr to 30 days post dose).

来源:Hazardous Substances Data Bank (HSDB)

代谢

...已鉴定出一个哺乳动物代谢物。这种代谢物被特征化为乙螨唑的N-去甲基化副产物。

...a single mammalian metabolite has been identified. This metabolite is characterized as an N-demethylation byproduct of emamectin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(3)H/(14)C标记的4"-脱氧-4"-表甲基氨基阿维菌素B1a（MAB1a）苯甲酸盐的代谢，这是阿维菌素类杀虫剂艾玛菌素苯甲酸盐的主要同系物（>/=90%），在产蛋鸡中进行研究。十只莱航鸡（Gallus domesticus）每天口服一次，连续7天（1 mg/kg体重/天）。每天收集鸡蛋和排泄物，随后将鸡蛋分离成蛋白和蛋黄。在最后一次给药后20小时内对鸡进行安乐死，并收集肝脏、肾脏、心脏、肌肉、脂肪、卵巢、肌胃、胃肠道及其内容物和尸体。大约70%和6%的总给药剂量分别在排泄物加胃肠道及其内容物和组织和鸡蛋中回收。确定了两个新的代谢物，即原化合物的24-羟甲基衍生物（24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a）和24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a的N-去甲基衍生物（24-羟甲基-4"-脱氧-4"-表氨基阿维菌素B1a）。此外，还分离并鉴定了这两种代谢物的八个脂肪酸结合物，这些结合物在组织和鸡蛋中的总放射性残留物中占8-75%。尽管这是迄今为止报道的对外源化学物质进行体内脂肪酸结合的最广泛研究之一，但由于本研究的给药水平大约是作物中MAB1a残留水平的1000倍，且大部分给药剂量在排泄物中回收，因此人类通过食用鸡肉接触MAB1a残留的风险极低。根据这些发现，MAB1a的禽类生物转化与哺乳动物的生物转化有显著差异。

The metabolism of (3)H/(14)C-labeled 4"-deoxy-4"-epimethylaminoavermectin B1a (MAB1a) benzoate, the major homologue (>/=90%) of the avermectin insecticide emamectin benzoate, was studied in laying chickens. Ten Leghorn hens (Gallus domesticus) were orally dosed once daily for 7 days (1 mg/kg of body weight/day). Eggs and excreta were collected daily, and eggs were subsequently separated into whites and yolks. Chickens were euthanized within 20 hr after the last dose, and liver, kidney, heart, muscle, fat, ovaries, gizzard, gastrointestinal tract and contents, and carcass were collected. Approximately 70 and 6% of the total administered dose were recovered in the excreta plus gastrointestinal tract and contents and in the tissues plus eggs, respectively. Two novel metabolites, i.e. the 24-hydroxymethyl derivative of the parent compound (24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a) and the N-demethylated derivative of 24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a (24-hydroxymethyl-4"-deoxy-4"-epiaminoavermectin B1a), were identified. In addition, eight fatty acid conjugates of each of these two metabolites, comprising 8-75% of total radioactive residues in tissues and eggs, were isolated and identified. Although this represents some of the most extensive in vivo fatty acid conjugation to a xenobiotic reported to date, potential human exposure to MAB1a residues from consumption of chicken would be extremely low, because the dosage level in this study was approximately 1000-fold greater than the MAB1a residue levels seen in crops and because the majority of the applied dose was recovered in the excreta. Based on these findings, the avian biotransformation of MAB1a differs substantially from the mammalian biotransformation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苜蓿夜蛾在哺乳动物中并不是广泛代谢的，有限的关于苜蓿夜蛾代谢物的信息表明，代谢不会导致苜蓿夜蛾的解毒。苜蓿夜蛾的一个植物代谢物比苜蓿夜蛾本身更具毒性。

While emamectin benzoate is not extensively metabolized in mammals, the limited information on the metabolites of emamectin benzoate suggests that metabolism does not result in the detoxification of emamectin benzoate. One plant metabolite of emamectin benzoate is somewhat more toxic than emamectin benzoate itself.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

家蝇（Musca domestica L.）是全球乳品作业的重要害虫，能够适应广泛的环境条件。目前有多种杀虫剂用于它们的防治，但抗药性的发展是一个严重的问题。杀虫剂混合使用可以提高杀虫剂对具有抗性的害虫的毒性，因此可能成为一种潜在的害虫抗药性管理工具。本研究评估了单独使用以及混合使用时， bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）、deltamethrin（溴氰菊酯）、chlorpyrifos（毒死蜱）、profenofos（丙氟磷）、emamectin benzoate（甲氨基阿维菌素苯甲酸盐）和fipronil（氟虫腈）对家蝇的毒性。与实验室敏感品系相比，现场收集的家蝇群体对所有调查的杀虫剂均表现出显著抗性。大多数杀虫剂混合物，如将一种拟除虫菊酯与其他化合物混合，在两种条件下（1:1-"A"和LC50:LC50-"B"）显著提高了拟除虫菊酯对现场群体的毒性。在这两种条件下，拟除虫菊酯与其他化合物的组合指数在大多数情况下显著低于1，表明存在协同作用。当酶抑制剂PBO和DEF与杀虫剂联合用于抗性群体时，bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）、deltamethrin（溴氰菊酯）和emamectin（甲氨基阿维菌素）的毒性显著提高，这表明存在酯酶和单加氧酶介导的抗性机制。通过将chlorpyrifos（毒死蜱）、profenofos（丙氟磷）、emamectin（甲氨基阿维菌素）和fipronil（氟虫腈）与之结合，可以提高抗性家蝇群体中bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）和deltamethrin（溴氰菊酯）的毒性。目前的研究结果可能对家蝇的抗药性管理具有实际意义。

House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1?1-"A" and LC50: LC50-"B") significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

早期中毒迹象包括瞳孔扩张、肌肉失调和肌肉震颤。在暴露后半小时内呕吐可以减少意外摄入产品后的毒性；在暴露后迅速（<15分钟）反复给予大量水中的医疗活性炭……。如果暴露引起的毒性进展到严重呕吐，应评估由此引起的液体和电解质失衡的程度。应根据临床迹象、症状和测量给予适当的支持性静脉补液替代疗法，以及其他必要的支持性措施（例如维持血压水平和适当的呼吸功能）。在严重病例中，应继续观察至少几天，直到临床状况稳定和正常。由于认为乙螨唑苯甲酸盐在动物中增强GABA活性，因此避免给有潜在毒性乙螨唑苯甲酸盐暴露的患者使用增强GABA活性的药物（巴比妥类药物、苯二氮卓类药物、丙戊酸）可能是明智的。

Early signs of intoxication include dilation of pupils, muscular incoordination, and muscular tremors. Vomiting within one-half hour of exposure can minimize toxicity following accidental ingestion of the product; rapidly after exposure (<15 minutes) administer repeatedly medical charcoal in a large quantity of water ... . If toxicity from exposure has progressed to cause severe vomiting, the extent of resultant fluid and electrolyte imbalance should be gauged. Appropriate supportive parenteral fluid replacement therapy should be given, along with other required supportive measures (such as maintenance of blood pressure levels and proper respiratory functionality) as indicated by clinical signs, symptoms, and measurements. In severe cases, observations should continue for at least several days until clinical condition is stable and normal. Since emamectin benzoate is believed to enhance GABA activity in animals, it is probably wise to avoid drugs that enhance GABA activity (barbiturates, benzodiazepines, valproic acid) in patients with potentially toxic emamectin benzoate exposure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒物A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

有两个给药组，每组由2只雄性比格犬组成。第1组在第1天接受0.5 mg/kg的(3)H-MK-0243苯甲酸盐（1 mL/kg在5%乙醇中……0.239 mCi/mg；98.8%放化学纯）给药，并在第15天接受0.5 mg/kg的(3)H-MK-0243 HCl（1 mL/kg在去离子水中……0.229 mCi/mg；98.7%放化学纯）给药。第2组的给药顺序相反。每次给药前测定体重。在每次给药后的0.5、1、2、4、6、8、24、48、96和168小时，分别抽取2 mL血液用于药物水平测定。在0至24小时和72至96小时收集尿液和粪便用于药物水平分析。没有发现药物效应。苯甲酸盐和HCl盐的平均血浆半衰期分别为35.7 +/- 3.4小时和35.5 +/- 4.4小时。苯甲酸盐和HCl盐的平均血浆近似曲线下面积（AUC）分别为4479 +/- 1476和4574 +/- 1514 ng/g血浆/7天。两种盐的平均血浆MAB1a（MK-0243的主要成分，占90至95%）水平约为100 ng当量/g血浆，在大约6小时出现峰值。在第1天和第4天，粪便和尿液中回收的总和约为剂量的40%和0.01%。结论是这两种盐在雄性比格犬中是生物等效的。

There were 2 dosing groups, each consisting of 2 male beagles. Group 1 received 0.5 mg/kg of (3)H-MK-0243 benzoate (1 mL/kg in 5% ethanol ... 0.239 mCi/mg; 98.8% radiochemically pure) on day 1 and 0.5 mg/kg of (3)H-MK-0243 HCl (1 mL/kg in deionized water ... 0.229 mCi/mg; 98.7% radiochemically pure) on day 15. Dosing was reversed for Group 2. Body weights were determined before each dose. 2 mL of blood was withdrawn for drug level determinations following each dose at 0.5, 1, 2, 4, 6, 8, 24, 48, 96 and 168 hr. Urine and feces were collected for drug level analysis at 0 to 24 and 72 to 96 hr. There was no evidence of drug effects. The mean plasma half lives for the benzoate and HCl salts were 35.7 +/- 3.4 hr and 35.5 +/- 4.4 hr, respectively. The mean plasma approximate area under the curve (AUC) for the benzoate and HCl salts was 4479 +/- 1476 and 4574 +/- 1514 ng/g plasma/7days. The mean peak plasma MAB1a (the major component of MK-0243 at 90 to 95%) levels were ~100 ng equivalents/g plasma, occurring at ~6 hr for either salt. Combined fecal and urine recoveries during the 1st and 4th days were ~40% and 0.01% of the dose, respectively. It is concluded that the 2 salts are bioequivalent in male beagle dogs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

实验性杀虫剂阿维菌素本贝酸盐的皮肤吸收在猕猴身上进行了研究。通过比较皮肤应用化合物的排泄物中放射性水平与等效静脉注射剂量后的放射性水平来计算皮肤吸收。给三只猴子静脉注射300微克(3)H-MAB1a（作为丙二醇：生理盐水的1:1溶液），血浆水平呈双相下降，在最初的15分钟内放射性迅速下降，随后以较慢的速度下降到背景水平。在给药后7天，大约90%和5%的给药放射性分别从粪便和尿液中回收。经过一段清洗期后，将300微克[(3)H]MAB1a（溶解在可乳化浓缩物中）涂抹在相同猴子剃光的 forearm 上。经过10小时的暴露期后，大约90%的放射性在暴露前臂的肥皂和水中清洗后被回收。尽管血浆放射性水平通常保持在背景水平以下，但大约1.5%的施用剂量在排泄物中被回收。阿维菌素本贝酸盐的皮肤吸收计算为1.6%。阿维菌素本贝酸盐的低皮肤渗透性表明，农业工人实际上接触到这种化合物的可能性很小。

The dermal absorption of the experimental avermectin insecticide emamectin benzoate was studied in the Rhesus monkey. Dermal absorption was calculated by comparing radioactivity levels in excreta following dermal application of the compound with those following administration of an equivalent intravenous dose. After iv administration of 300 ug (3)H-MAB1a (prepared as a 1:1 solution of propylene glycol:saline) to three monkeys, plasma levels decreased biphasically with a rapid decline in radioactivity during the first 15 min followed by a slower decline to background. By 7 days post-dose, approximately 90% and 5% of the administered radioactivity was recovered in the feces and urine, respectively. After a washout period, 300 micrograms [(3)H]MAB1a (dissolved in emulsifiable concentrate) was applied topically to the shaved forearm of the same monkeys. Following a 10-hr exposure period, approximately 90% of the radioactivity was recovered in a soap and water wash of the exposed forearms. Although plasma radioactivity levels generally remained below background levels, approximately 1.5% of the applied dose was recovered in the excreta. Dermal absorption of [()3H]emamectin benzoate was calculated as 1.6%. The low dermal penetration of emamectin benzoate indicates that minimal actual exposure of agricultural workers to this compound will occur.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这项研究的目标是调查在推荐剂量给药后血液、粘液和肌肉中的埃玛菌素含量，以及与同一条鱼上的海虱感染的相关性（消除研究）。通过全身自动放射性显影和闪烁计数法，还研究了单次口服给药后大西洋鲑鱼体内三标埃玛菌酸苄酯的组织分布（分布研究）。在消除研究中，埃玛菌酸苄酯的浓度在第7天，即给药的最后一天，分别在血液、粘液和肌肉中达到最高水平，分别为128、105和68纳克/克（ppb）。从第7天开始，血液中的浓度下降，直到第77天浓度低于检测限。除了第7天和第21天，粘液中的浓度高于血浆（P < 0.05）。埃玛菌酸苄酯的浓度从治疗结束（第7天）逐渐下降到第70天，肌肉、血浆和粘液的半衰期分别为9.2、10.0和11.3天。分布研究表明，在整个观察期（56天）内，粘液膜（胃肠道、鳃）中的放射性活性很高。在整个研究期间，松果体、垂体和嗅囊的活性很高。胆汁中的活性最高，表明这是排泄的重要途径。分布研究确认了消除研究中关于血液、皮肤粘液和肌肉中浓度的结果。

The aims of this study were to investigate the content of emamectin in blood, mucus and muscle following field administration of the recommended dose, and correlation with sea lice infection on the same fish (elimination study). The tissue distribution of tritiated emamectin benzoate after a single oral dose in Atlantic salmon was also investigated by means of whole-body autoradiography and scintillation counting (distribution study). In the elimination study, concentrations of emamectin benzoate reached maximum levels of 128, 105 and 68 ng/g (p.p.b.) for blood, mucus and muscle respectively, on day 7, the last day of administration. From day 7, the concentration in the blood declined until concentration was less than the limit of detection on day 77. The concentration was higher in mucus compared with plasma (P < 0.05) except on days 7 and 21. The concentration of emamectin benzoate decreased gradually from the end of treatment (day 7) to day 70 with half-lives of 9.2, 10.0 and 11.3 days in muscle, plasma and mucus respectively. The distribution study demonstrated a high quantity of radioactivity in mucous membranes (gastrointestinal tract, gills) throughout the observation period (56 days). Activity was high in the epiphysis, hypophysis and olfactory rosette throughout the study. The highest activity was observed in the bile, indicating this to be an important route for excretion. The distribution study confirmed the results from the elimination study with respect to concentrations in blood, skin mucous and muscle.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大西洋鲑鱼（约1.3公斤）在5±1摄氏度的海水罐中饲养，通过饲料以名义上的50微克/公斤/天的剂量给予3H-埃玛菌素B1苄酯，连续7天。在最后给药后的3小时和12小时以及1、3、7、15、30、45、60和90天，从每组10条鱼中收集组织、血液和胆汁。从最后给药前的罐中开始，每天收集粪便，直至最后给药后90天。在给药期间，每日粪便样本的总放射性残留物（TRR）最大为0.25 ppm，且在覆盖给药期的合并粪便中，大于97%的TRR是埃玛菌素B1a。粪便TRR随后迅速下降，到最后给药后1天大约为0.05 ppm。90天给药期间组织平均TRR的范围如下：肾脏，1.4-3 ppm；肝脏，1.0-2.3 ppm；皮肤，0.04-0.09 ppm；肌肉，0.02-0.06 ppm；骨骼，<0.01 ppm。按给药间隔合并的肝脏、肾脏、肌肉和皮肤样本的残留成分是埃玛菌素B1a（81-100% TRR）和去甲基埃玛菌素B1a（0-17% TRR），在一些肌肉样本中可以看到N-甲酰埃玛菌素B1a的微量（<2%）。选作埃玛菌素残留监管监测的标志残留物是埃玛菌素B1a。使用HPLC-荧光法在皮肤和肌肉的个别样本中定量埃玛菌素B1a水平，在所有分析的样本中（给药后3小时至30天），埃玛菌素B1a水平均低于85 ppb。

Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with 3H-emamectin B1 benzoate in feed at a nominal rate of 50 ug of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 hr and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 hr to 30 days post dose).

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

阿维菌素衍生品

埃玛菌素（emamectin，又称甲氨基阿维菌素）是以阿维菌素为母体通过半合成进行结构改造而开发出的一系列活性更高、选择性更强、安全性更优的衍生新品种。最初，阿维菌素主要用作驱寄生虫药剂，尽管它是一种优秀的兽用驱虫剂，但由于其经皮毒性很低但人畜口服毒性较高，做成口服剂时存在一个矛盾：用量太低效果不好，而用量太高则安全性不足。为了改善这一不足，默克公司对其化学结构进行了改造，从中筛选出了两个新的化合物即伊维菌素和埃玛菌素。

作用机理

伊维菌素明显地改善了人畜的急性口服毒性，因此兽用阿维菌素驱虫剂现在通常使用的是伊维菌素成分。埃玛菌素则扩大了阿维菌素的杀虫谱并克服了阿维菌素对鳞翅目害虫效果不佳的问题。埃玛菌素的制剂苯甲酸盐即为甲维盐，因此伊维菌素和甲维盐可视为原来阿维菌素的升级改良产品。伊维菌素毒性较低，主要用于动物（且其结构更稳定，也是全球销量最大的阿维菌素系列之一）。相比之下，甲维盐活性比阿维菌素高很多（胃毒毒性是阿维菌素的2146倍），尤其对鳞翅目、双翅目和蓟马类害虫表现出极高的活性。例如，对于斜纹夜蛾等鳞翅目害虫，阿维菌素效果不佳，但甲维盐却是特效药。

适用作物

埃玛菌素适用于蔬菜、果树、烟草、茶树、花卉及大田作物（如水稻、棉花、玉米、小麦和大豆等）。

防治对象

甲维盐对多种害虫具有其他农药无法比拟的活性，尤其对鳞翅目、双翅目和蓟马类害虫效果超群。具体防治对象包括红带卷叶蛾、烟蚜夜蛾、棉铃虫、烟草天蛾、小菜蛾黏虫、甜菜夜蛾、旱地贪夜蛾、纷纹夜蛾、甘蓝银纹夜蛾、菜粉蝶、菜心螟、甘蓝横条螟、番茄天蛾、马铃薯甲虫、墨西哥瓢虫、红蜘蛛和食心虫等。

合成方法

甲氨基阿维菌素可从一种天然的土壤放射菌——链霉菌的发酵分离得到。

反应信息

• 作为反应物：
  描述：

  emamectin 、 苯甲酸 在 溶剂黄146 作用下， 以98.58 %的产率得到emamectin benzoate
  参考文献：
  名称：

  一种甲维盐及其中间体的合成工艺

  摘要：

  本发明涉及一种甲维盐及其中间体的合成工艺，其中，所述甲维盐中间体的合成工艺包括胺化反应，所述胺化反应是以阿维菌素的氧化产物AVMBC4"＝O为原料，在胺化试剂和胺化催化剂的作用下，发生胺化反应，生成亚胺化产物AVMBC4"＝NCH3，即甲维盐中间体；其中，所述胺化催化剂采用醋酸铵。本发明以醋酸铵作为胺化反应的催化剂，解决了因三氟乙酸锌作为催化剂而带来的一些列问题。

  公开号：

  CN117486947A
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 四(三苯基膦)钯 作用下， 以 乙醇 为溶剂， 以95.34 %的产率得到emamectin
  参考文献：
  名称：

  一种甲维盐及其中间体的合成工艺

  摘要：

  本发明涉及一种甲维盐及其中间体的合成工艺，其中，所述甲维盐中间体的合成工艺包括胺化反应，所述胺化反应是以阿维菌素的氧化产物AVMBC4"＝O为原料，在胺化试剂和胺化催化剂的作用下，发生胺化反应，生成亚胺化产物AVMBC4"＝NCH3，即甲维盐中间体；其中，所述胺化催化剂采用醋酸铵。本发明以醋酸铵作为胺化反应的催化剂，解决了因三氟乙酸锌作为催化剂而带来的一些列问题。

  公开号：

  CN117486947A

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [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。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
• [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。
• THIENYLPYRIDYLCARBOXAMIDES
  申请人：Dunkel Ralf

  公开号：US20110105564A1

  公开（公告）日：2011-05-05

  Novel thienylpyridylcarboxamides of the formula (I) The present application is also directed to a plurality of processes for preparing these compounds and their use for controlling unwanted microorganisms, and also novel intermediates and their preparation.

  新型噻吩基吡啶基羧酰胺的化学式（I） 本申请还涉及多种制备这些化合物的方法，以及它们用于控制不受欢迎的微生物的用途，还有新颖的中间体及其制备。