3-碘-N'-(2-甲磺酰基-1,1-二甲基乙烷基-N-{4-[1,2,2,2-四氟-1-(三氟甲基)乙基]-0-甲苯基}邻苯二酰胺 | 272451-65-7

• 物质功能分类: 分析化学 - 标准品 - 农残、兽药及化肥类
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-碘-N'-(2-甲磺酰基-1,1-二甲基乙烷基-N-{4-[1,2,2,2-四氟-1-(三氟甲基)乙基]-0-甲苯基}邻苯二酰胺
• 中文别名: 氟虫双酰胺；垄歌；氟苯虫酰胺
• 英文名称: flubendiamide
• 英文别名: 3-iodo-N'-(2-mesyl-1,1-dimethylethyl)-N-{4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-o-tolyl}phthalamide；N2-[1,1-dimethyl-2-(methylsulfonyl)ethyl]-3-iodo-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl) ethyl]phenyl]-1,2-benzenedicarboxamide；1-N-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-2-methylphenyl]-3-iodo-2-N-(2-methyl-1-methylsulfonylpropan-2-yl)benzene-1,2-dicarboxamide
• CAS: 272451-65-7
• 化学式: C₂₃H₂₂F₇IN₂O₄S
• 分子量: 682.398
• InChiKey: ZGNITFSDLCMLGI-UHFFFAOYSA-N

物化性质

• 熔点：
  218-221 °C
• 沸点：
  578.6±50.0 °C(Predicted)
• 密度：
  1.615±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• LogP：
  3.250 (est)
• 颜色/状态：
  White crystalline powder
• 蒸汽压力：
  <7.5X10-7 mm Hg at 25 °C
• 自燃温度：
  435 °C/ 815 °F. /Belt SC Insecticide/
• 解离常数：
  Does not dissociate

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  11

ADMET

代谢

通常情况下，每组4只非禁食的大鼠/性别，每天通过灌胃方式给药14天的氟苯二酰胺（NNI-0001），在邻苯二甲酸环上标记有（14）C，纯化后的放射性纯度为99.2%，在水悬浮液中含有2%的羧甲基纤维素钠和0.4%的Tween 80。本研究评估了包括主要代谢物量化在内的ADME特性。在大鼠最后一次（第14次）给药后9小时、24小时或168小时对其进行处死。...雌性大鼠的代谢标签较少，且比雄性大鼠在长期组织中的标签保留量更大，与其他研究一致。母氟苯二酰胺在雄性和雌性粪便代谢物中分别占82%和91%。剩余粪便标签的相对比例包括苯甲醇代谢物（A-16）（占雄性排泄放射活性的7.2%，雌性的2.2%）、苯甲酸代谢物（A-18）（占雄性排泄放射活性的2.8%，雌性中未检出），其他代谢物未被表征或含量非常小。本研究报告了在脂肪中可量化的大鼠碘磷酰亚胺代谢物（A-14）的量。这种代谢物涉及切割磷酰亚胺氮远处所有组分，但在排泄物中尚未发现可测量的量。

Typically sets of 4 non-fasted rats/sex were gavage-dosed daily for 14 days with Flubendiamide (NNI-0001), (14)C-labeled on the phthalic acid ring, radiochemical purity after purification of 99.2%, in an aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80. This study assessed ADME features including quantification of major metabolites. Rats were sacrificed either 9 hr, 24 hr, or 168 hr after the final (14th) dosing. ... Females showed less metabolized label and greater longterm tissue retention of label than males, consistent with other studies. Parent flubendiamide comprised 82% and 91% of fecal metabolites in males and females, respectively. Relative proportions of remaining fecal label consisted of the benzyl alcohol metabolite (A-16) (7.2% of excreted radioactivity in males, and 2.2% in females), the benzoic acid metabolite (A-18) (2.8% of excreted radioactivity in males and below detection in females), with other metabolites uncharacterized or in very small amounts. This study reported quantifiable amounts of the iodophthalimide metabolite (A-14) of flubendiamide in fat. This metabolite, involving cleavage of all components distal to the phthalamide nitrogen, had not been found in measurable amounts in excreta.

来源:Hazardous Substances Data Bank (HSDB)

代谢

通常，每组4只/性别的禁食大鼠一次通过灌胃给予氟苯二酰胺（NNI-0001），在酞酸环上或（在有限程度上）在苯胺环上标记（14）C，净化后的放射化学含量> 99.5%，在含有0.2% Tween 80的1%羧甲基纤维素钠水悬浮液中。本研究评估了ADME特征，包括用2或200 mg/kg氟苯二酰胺处理后主要代谢物的鉴定。标签在呼出空气中的排泄量没有明显差异。超过90%的给药剂量通过粪便排出，与剂量或性别无关。尽管尿液是一个小途径（< 2%的给药剂量），但雄性在尿液中的标签传递始终高于雌性。高剂量水平导致吸收明显减少。两种标记形式的排泄模式和代谢物色谱图之间没有明显差异，这表明分子的大部分之间几乎没有裂解。血液和血浆的Tmax为6至12小时。标签的组织分布主要在大肠、肝脏和其他高灌注器官以及体脂中。低剂量治疗发现，雄性组织的峰值水平比雌性高几倍。从9小时到24小时，雄性组织的水平降低了约90%，从24小时到168小时又降低了约90%。然而，雌性没有像雄性那样迅速清除组织，因此168小时后雌性的残留组织浓度高于雄性。氟苯二酰胺上可供氧化的主要取代基是苯胺环上的甲基。最常见的产品是那个甲基碳的苄醇（标为A-16）和苯甲酸（标为A-18）。较少的中间物苯甲醛被标为A-17。在代谢轮廓上出现了实质性的性别差异。在2 mg/kg雄性的粪便中，苄醇是主要的代谢物（占给药剂量的31-37%），其次是亲代氟苯二酰胺（占给药剂量的15-30%）和苯甲酸代谢物（占给药剂量的15-16%）。在2 mg/kg雌性的粪便中，66%的给药剂量是氟苯二酰胺，5-6%的给药剂量是苄醇，几乎没有苯甲酸代谢物。没有其他主要代谢物。在200 mg/kg时，两种性别的粪便中主要的标记成分是亲代氟苯二酰胺，这表明吸收是饱和的。雌性大鼠清除放射性的速度非常慢：对比2 mg/kg雄性在9小时和168小时后剂量后肝脏标签含量从5.628%降至0.104%的给药剂量，而雌性在相同的采样时间点为1.623%和1.305%的给药剂量。雌性大鼠对氟苯二酰胺的肝脏代谢能力有限，因此24小时时雌性肝脏中积累了相当数量的亲代氟苯二酰胺（比所有可提取代谢物组合的数量级多）。在雄性中，肝脏中几乎没有发现亲代氟苯二酰胺（不到苯甲醇或苯甲醛代谢物所占剂量的半数）。雄性肝脏中有较小但可测量的两种环结构之间裂解的唯一识别产物（苯胺片段）。

Typically sets of 4 fasted rats/sex were dosed once by gavage with Flubendiamide (NNI-0001), (14)C-labeled on either the phthalic acid ring or (to a limited extent) on the aniline ring, radiochemical content after purification > 99.5%, in an aqueous suspension of 1% sodium carboxymethylcellulose containing 0.2% Tween 80. This study assessed ADME features including identification of major metabolites following treatment with either 2 or 200 mg/kg flubendiamide. There was no significant excretion of label into expired air. Over 90% of administered dose was excreted in feces regardless of dose or sex. Although urine was a minor route (< 2% of administered dose), males consistently passed more label in urine than did females. High dose levels led to markedly reduced absorption. There was no obvious difference in excretion patterns and there were minimal differences in metabolite chromatograms between the two labeled forms, indicating that there was very little cleavage dividing major portions of the molecule. Tmax was 6 to 12 hours for blood and plasma. Tissue distribution of label was preferentially to the g.i. tract, liver and other highly perfused organs, and body fat. Low dose treatments found peak tissue levels in males several-fold higher than females. Tissue levels in males were lower by about 90% from 9 hrs to 24 hrs, and by another 90% from 24 hrs to 168 hrs. Females did not clear tissues as rapidly as males, however, so females had higher residual tissue concentrations at 168 hours than males. The primary substituent available for oxidation on flubendiamide is the methyl group on the aniline ring. The most common products were the benzyl alcohol (designated A-16) and the benzoic acid (designated A-18) of that methyl carbon. The less abundant intermediate benzaldehyde was designated as A-17. Substantial sex differences emerged in metabolic profiles. In the feces, the benzyl alcohol was the dominant metabolite in 2 mg/kg males (31-37% of administered dose), followed by parent flubendiamide (15-30% of administered dose), and the benzoic acid metabolite (15-16% of administered dose). In feces of 2 mg/kg females, 66% of administered dose was flubendiamide, 5-6% of administered dose was benzyl alcohol, and there was very little benzoic acid metabolite. There were no other major metabolites. Parent flubendiamide was the predominant labeled constituent in feces of both sexes at 200 mg/kg, indicating saturable absorption. Female rats were very slow to clear radioactivity: contrast liver label content in 2 mg/kg males dropping from 5.628% to 0.104% of administered dose at 9 hrs and 168 hrs after dosing vs. content in females of 1.623% and 1.305% of administered dose at the same sampling times. Female rats have limited hepatic metabolic capacity for flubendiamide, hence there was appreciable accumulation of parent flubendiamide in the livers of females at 24 hours (an order of magnitude more than all extractable metabolites combined). In males, very little parent flubendiamide was found in liver (less than half of the percent of dose represented by benzyl alcohol or benzaldehyde metabolites). Liver in males had smaller but measurable amounts of the sole identified product of cleavage between the two ring structures of flubendiamide (the aniline fragment).

来源:Hazardous Substances Data Bank (HSDB)

代谢

氟苯尼胺（纯化至99.6%，用于非标记活性成分和邻苯二甲酸环上标记的14C）通过一次灌胃给药（含2%羧甲基纤维素钠的水悬浮液，含0.4%吐温80）给予安装了胆管导管的F-344（F344/DuCrj）大鼠。在最终研究中，3只雄性和6只雌性接受了2 mg/kg的剂量。（为了促进代谢物特征的分析，额外的大鼠在16小时间隔内两次给药，每次20 mg/kg活性成分。）……在粪便或胃肠道内容物中观察到的唯一可定量代谢物是苯甲醇代谢物，可能是由于肠道微生物对未被吸收物质的作用。雄性大鼠胆汁中的大部分成分是苯环上甲基基团的氧化产物……。邻苯二甲酰胺氮和磺酰基团之间的甲基基团也有一些氧化（包括研究者指定的A-19、A-20、A-25和A-29的化合物）。最常见的是，苯环上甲基基团的氧化产物并未结合，然而看起来邻苯二甲酰胺氮和磺酰基团之间的甲基基团的氧化在雄性中常常随后发生葡萄糖醛酸结合。两性大鼠都能形成亲本化合物的谷胱甘肽结合物，研究者提出这种结合是在邻苯二甲酸环上。在雌性中，谷胱甘肽结合物（以及结合的下游衍生物）是主要的胆汁代谢物。在胆汁中观察到了一种环状缩醛，尤其是在雄性中。

Flubendiamide (purified to 99.6% purity for non-labeled a.i. and for (14)C-labeled on the phthalic acid ring) was administered once by gavage (aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80) to F-344 (F344/DuCrj) rats provided with biliary cannulae. Three males and 6 females received 2 mg/kg in the definitive study. (Additional rats were dosed twice at 16-hr intervals with 20 mg/kg a.i. to facilitate characterization of metabolites.) ... The only quantifiable metabolite observed in feces or gastrointestinal content was the benzyl alcohol metabolite, possibly resulting from intestinal microbial action of non-absorbed material. Much of the biliary profile in males consisted of oxidation products of the methyl group on the aniline ring ... . There was also some oxidation of the methyl groups between the phthalamide nitrogen and the sulfonyl group (including compounds designated A-19, A-20, A-25, and A-29 by investigators). Most commonly the oxidation products of the methyl group on the aniline ring were not conjugated, however it appears that oxidation of a methyl group between the phthalamide nitrogen and the sulfonyl group frequently was followed by glucuronide conjugation in males. Both sexes were capable of glutathione formation of parent compound, conjugation proposed by investigators to be on the phthalic ring. In females, glutathione conjugates (and downstream derivatives of the conjugation) were the dominant biliary metabolites. A cyclic acetal was observed in bile, particularly in males.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大鼠、狗、小鼠和人类的微体（所有物种中均包括两性）都能够将氟苯二酰胺代谢为A-16，除了雌性大鼠的微体。 (人类微体，而不是大鼠微体，另外还产生了少量的羟基苯甲酸代谢物A-20，然而代谢为A-16似乎是一个有效的整体氟苯二酰胺代谢指标。) 在雄性大鼠微体中测试了对细胞色素P450同型的抗血清，发现抗CYP3A2血清对A-16的产生没有影响，而抗CYP2C11显著抑制了A-16的产生。相比之下，表达大鼠CYP3A2的重组微体产生了A-16，而其他同型包括CYP2C11的重组微体则没有。对人类肝微体活性的抗体的研究发现，抗大鼠CYP3A2和抗人CYP3A4在男性和女性人类肝脏的微体中引起了相似和实质性的抑制（注意到抗大鼠CYP3A2对CYP3A4有强烈的反应性）。在评估A-16产生的5种表达人类肝P450同型的重组微体中，只有CYP3A4产生了可测量的A-16。

Rat, dog, mouse, and human microsomes (from both sexes in all species) were all able to metabolize flubendiamide to A-16, except for microsomes from female rats. (Human microsomes, but not rat microsomes, additionally produced small amounts of hydroxybenzoic acid metabolite, A-20, however metabolism to A-16 appears to be a valid indicator of overall flubendiamide metabolism.) Antisera to CYP isoforms tested in male rat microsomes found that anti-CYP3A2 sera had no effect on A-16 production, whereas anti-CYP2C11 markedly inhibited A-16 production. In contrast, recombinant microsomes expressing rat CYP3A2 produced A-16, whereas other isoforms including CYP2C11 recombinant microsomes did not. Antibody effects on human liver microsome activities found that anti-rat CYP3A2 and anti-human CYP3A4 caused similar and substantial inhibition in microsomes from male or female human liver (it was noted that anti-rat CYP3A2 was strongly reactive toward CYP3A4). Of 5 recombinant microsomes expressing human liver P450 isoforms evaluated for A-16 production, only CYP3A4 yielded measurable A-16.

来源:Hazardous Substances Data Bank (HSDB)

代谢

F-344（F344/DuCrj）大鼠和Crlj: CD1（ICR）小鼠（每种类别、性别和给药期4只）以200 mg/kg/天的剂量经灌胃给予纯度为96.7%的非标记氟虫酰胺，溶剂为玉米油。治疗持续1、7或14天。动物在最后一次给药后24小时被处死。...测定了血浆、肝脏和脂肪中氟虫酰胺及其碘磷酰亚胺代谢物（A-14）的浓度。在雄性动物中，氟虫酰胺在这些组织中随时间增加不明显。雌性动物在所有研究组织中都有轻微的积累，到第7天达到稳态。A-14在大鼠两性脂肪中似乎都有积累，到第7天达到稳态。氟虫酰胺在肝脏和脂肪中的浓度总是高于血浆，且雌性动物中的浓度远高于雄性。第7天，雄性大鼠肝脏和脂肪中的氟虫酰胺浓度分别为1.3和8.9 mg/kg。雌性大鼠肝脏和脂肪中的浓度为26.7和68.0 mg/kg。第7天，雄性和雌性大鼠肝脏和脂肪中的A-14浓度分别为< 1.0和2.9 mg/kg。第7天，雄性小鼠肝脏和脂肪中的氟虫酰胺浓度为2.3和3.4 mg/kg。相应地，雌性小鼠的浓度为2.4和1.9 mg/kg（即与雌性大鼠显著的积累情况大不相同）。A-14在雄性和雌性小鼠中的水平通常低于定量限。本研究表明，雌性大鼠对氟虫酰胺的代谢能力有限，并且倾向于代谢大量A-14的情况并不适用于小鼠的任何性别。

F-344 (F344/DuCrj) rats and Crlj: CD1 (ICR) mice (4/species/sex/dosing period) were dosed with 200 mg/kg/day unlabeled flubendiamide, purity 96.7% by gavage in corn oil. Treatments were daily for 1, 7, or 14 days. Animals were sacrificed 24 hr after the final dose. ...Concentrations of flubendiamide and of the iodophthalimide metabolite (A-14) /were determined/ in plasma, liver, and fat. Flubendiamide did not increase in these tissues over time in males. There was a marginal accumulation in females in all studied tissues, reaching steady state by day 7. A-14 appeared to be accumulating in fat in rats of both sexes, reaching steady state by day 7. Flubendiamide was always more concentrated in liver and fat than in plasma, and concentrations were much higher in females than in males. Day 7 concentrations of flubendiamide in liver and fat of male rats at day 7 were 1.3 and 8.9 mg/kg, respectively. Liver and fat concentrations in female rats were 26.7 and 68.0 mg/kg. A-14 concentrations in male and female rats for liver and fat at day 7 were identical at < 1.0 and 2.9 mg/kg, respectively. Flubendiamide concentrations on day 7 in liver and fat of male mice were 2.3 and 3.4 mg/kg, respectively. Corresponding levels in female mice were 2.4 and 1.9 mg/kg (i.e. much unlike the marked accumulation in female rats). A-14 levels were generally below quantification limits in both male and female mice. This study indicates that limited metabolic capacity of female rats toward flubendiamide and tendency to metabolize significant amounts of A-14 do not apply to either sex of mice.

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和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，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。如果患者呕吐，让患者向前倾或将其置于左侧（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。寻求医疗救助。 /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，辅助通气。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……。预防癫痫发作，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……。/毒药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"，最低流量/。如果出现低血容量的迹象，使用0.9%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)

毒理性

• 非人类毒性摘录

实验室动物：亚慢性或前慢性暴露 NNI-0001（/flubendiamide/，纯度=97.1%）应用于每剂量每组10只Fischer（F344/NHsd）大鼠的剃毛背部皮肤，剂量水平为0（自来水）、10、100或1000 mg/kg/天，每天6小时，每周5天，持续4周（第4周每周7天）。没有发生与治疗相关的死亡。没有观察到临床体征。开阔场地观察未发现异常。检查体重和食物消耗数据未发现与治疗相关的效果。血液学数据没有显示明确的剂量-反应关系。血清化学数据没有显示生物学上的显著变化。尿液分析未发现与治疗相关的效果。在1000 mg/kg/天的剂量下，两性的平均相对肝重量有治疗相关的增加。宏观检查未发现与治疗相关的异常。显微镜检查发现，在1000 mg/kg/天的剂量下，肝脏门脉周围区域的脂肪阳性反应升高（女性在发生率上，男性和女性在严重程度上）。此外，在1000 mg/kg/天的剂量下，女性甲状腺滤泡细胞肥大的发生率较高。... NOEL（男/女，系统性）= 100 mg/kg/天（基于平均相对肝重量增加和肝脏和甲状腺的组织病理学变化）。NOEL（男/女，皮肤效果）= 1000 mg/kg/天（基于在最高测试剂量下未观察到效果）。

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ NNI-0001 (/flubendiamide/, purity = 97.1%) was applied to the shaved dorsal skin of 10 Fischer (F344/NHsd) rats per sex per dose at dose levels of 0 (tap water), 10, 100, or 1000 mg/kg/day for 6 hours per day 5 days per week for 4 weeks (7 days per week during the 4th week). No treatment-related mortalities occurred. No clinical signs were observed. Open field observations revealed no abnormalities. Examination of body weight and food consumption data revealed no treatment-related effects. Hematological data revealed no clear dose-response relationship. Serum chemistry data revealed no biologically significant changes. Urinalysis revealed no treatment-related effects. A treatment-related increase in mean relative liver weight was observed in both sexes at 1000 mg/kg/day. Macroscopic examination revealed no treatment-related abnormalities. Microscopic examination revealed a treatment-related elevated fat positive reaction (in incidence in females and in severity in males and females) in the periportal zone of the liver at 1000 mg/kg/day. Also, a treatment-related higher incidence of follicular cell hypertrophy in the thyroid was observed in females at 1000 mg/kg/day. ... NOEL (M/F, systemic) = 100 mg/kg/day (based on increased mean relative liver weights and histopathological changes in the liver and thyroid). NOEL (M/F, skin effects) = 1000 mg/kg/day (based on no effects at the highest dose tested).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验动物：亚慢性或前慢性暴露 NNI-0001（/flubendiamide/，纯度=98.5%）被混合到饲料中，以每剂量每组4只性别各异的比格犬进行喂养，剂量水平为0、100、2000或40000 ppm（分别为雄性0、2.58、52.7和1076 mg/kg/天，雌性0、2.82、59.7和1135 mg/kg/天），连续喂养90天。没有发生死亡。在40000 ppm剂量下，两种性别都观察到了与治疗相关的松散粪便。检查体重和食物消耗量数据未发现与治疗相关的效果。尿液分析未发现与剂量相关的效果。在2000和40000 ppm剂量下的第4、8和13周，两种性别的平均活化部分凝血活酶时间观察到与治疗相关的下降。在40000 ppm剂量下的第4、8和13周，雄性中的平均总碱性磷酸酶水平观察到与治疗相关的增加，在雌性的2000和40000 ppm剂量下也是如此。此外，在40000 ppm剂量下的第4和8周，雄性中的平均胆固醇水平观察到与治疗相关的下降，在雌性的2000和40000 ppm剂量下的第4、8和13周，平均甘油三酯水平观察到与治疗相关的增加。在40000 ppm剂量下，两种性别的平均相对肾上腺重量有增加的趋势。宏观检查未发现与治疗相关的异常。微观检查发现在40000 ppm剂量下的雄性和2000及40000 ppm剂量下的雌性肾上腺皮质细胞有与治疗相关的肥大。...根据碱性磷酸酶活性增加、活化部分凝血活酶时间减少、平均相对肾上腺重量增加的趋势以及肾上腺皮质细胞的肥大，NOEL（M）= 2.58 mg/kg/天（100 ppm）和NOEL（F）= 2.82 mg/kg/天（100 ppm）。

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ NNI-0001 (/flubendiamide/, purity = 98.5%) was admixed to the diet and fed to 4 beagle dogs per sex per dose at dose levels of 0, 100, 2000, or 40000 ppm (0, 2.58, 52.7, and 1076 mg/kg/day, respectively for males and 0, 2.82, 59.7, and 1135 mg/kg/day, respectively for females) continuously for 90 days. No mortalities occurred. Treatment-related loose stool was observed in both sexes at 40000 ppm. Examination of body weight and food consumption data revealed no treatment-related effects. Urinalysis revealed no dose-related effects. A treatment-related decrease in mean activated partial thromboplastin time was observed at weeks 4, 8, and 13 in both sexes at 2000 and 40000 ppm. A treatment-related increase in the mean total alkaline phosphatase level was observed at weeks 4, 8, and 13 in males at 40000 ppm and in females at 2000 and 40000 ppm. Also, a treatment-related decrease in mean cholesterol levels in males at 40000 ppm at weeks 4 and 8 and a treatment-related increase in mean triglyceride levels in females at 2000 and 40000 ppm at weeks 4, 8, and 13 were observed. A trend toward increased mean relative adrenal weights was observed in both sexes at 40000. Macroscopic examination revealed no treatment-related abnormalities. Microscopic examination revealed treatment-related hypertrophy of the cortical cells of adrenals in males at 40000 and in females at 2000 and 40000 ppm. ... NOEL (M) = 2.58 mg/kg/day (100 ppm) and NOEL (F) = 2.82 mg/kg/day (100 ppm) based on an increase in alkaline phosphatase activity, decreased activated partial thromboplastin time, a trend toward increased mean relative adrenal weights, and hypertrophy of the cortical cells of adrenals.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氟苯尼考（提纯至99.6%纯度，用于非标记活性成分和标记在邻苯二甲酸环上的(14)C）通过一次灌胃给药（含有0.4% Tween 80的2%羧甲基纤维素钠水悬浮液）给予安装了胆管插管的F-344（F344/DuCrj）大鼠。在确定性研究中，3只雄性和6只雌性大鼠接受了2 mg/kg的剂量。（为了促进代谢物特征的分析，额外的老鼠在16小时间隔内两次给药20 mg/kg活性成分。）研究者们确定了48小时内胆汁、尿液、粪便中的标记物排泄情况，并测定了胃肠道内容物、冲洗后的胃肠道、肝脏以及残留尸体中的残留物。研究者们还确定了48小时胆汁、粪便和胃肠道内容物中的主要代谢物。吸收速度缓慢：48小时时，雄性和雌性大鼠胃肠道内容物中分别含有60%和51%的给药标记物。胆汁中分别含有11.1%和3.3%的给药标记物。这些插管大鼠的粪便中分别含有12.8%和11.0%的给药标记物。尿液中的给药标记物仅占0.75%和0.15%，因此在本研究中未评估尿液中的代谢物。母体氟苯尼考是两性（粪便加胃肠道内容物）中的主要成分（从这些来源中回收的标记物在雄性中占94%，在雌性中占99%）...

Flubendiamide (purified to 99.6% purity for non-labeled a.i. and for (14)C-labeled on the phthalic acid ring) was administered once by gavage (aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80) to F-344 (F344/DuCrj) rats provided with biliary cannulae. Three males and 6 females received 2 mg/kg in the definitive study. (Additional rats were dosed twice at 16-hr intervals with 20 mg/kg a.i. to facilitate characterization of metabolites.) Investigators determined the excretion of label in bile, urine, feces over 48 hours, and determined the residues in gastrointestinal tract contents, in the rinsed gastrointestinal tract, the liver, and in residual carcass. Investigators also identified the major metabolites in bile, feces, and gastrointestinal tract contents at 48 hours. Absorption was slow: contents of the gastrointestinal tract at 48 hours contained 60% and 51% of administered label in males and females, respectively. Bile contained 11.1% and 3.3% of administered label in males and females, respectively. Feces in these cannulated rats contained 12.8% and 11.0% of administered label in males and females. Urine contained only 0.75% and 0.15% of administered label in males and females: thus urinary metabolites were not assessed in this study. Parent flubendiamide was the dominant component of (feces plus gastrointestinal content) in both sexes (94% of label recovered from these sources in males, and 99% in females). ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

通常情况下，每组4只非禁食的大鼠/性别，每天通过灌胃方式给药14天的氟苯尼胺（NNI-0001），在邻苯二甲酸环上标记为（14）C，纯化后的放射化学纯度为99.2%，在含有0.4% Tween 80的2%羧甲基纤维素钠的水悬浮液中。本研究评估了包括主要代谢物量化在内的ADME特征。在大鼠最后一次（第14次）给药后9小时、24小时或168小时对其进行处死。目前的研究结果应与主要的单次给药研究（DPR文件编号53013-0179，记录编号226611）进行比较。当比较1次、6次或13次每日给药后24小时采样的大鼠时，血液或血浆水平没有实质性变化。在连续给药14天后，从9小时到168小时的组织分布发现，与单次给药研究相比，本研究中标签在最初24小时内通过胃肠道的移动较慢。在本研究的24小时内，与单次给药研究相比，更多的标签留在了肠道内容物中。此外，与单次给药研究相比，本研究在给药后9小时到24小时内，组织水平下降的速度并不快。给药后7天，两个研究的组织水平相当。根据尿液中检测到的给药标签的百分比，目前研究的整体吸收似乎明显低于单次给药研究观察到的水平。这反映出对非禁食动物给药的吸收相对较低。...

Typically sets of 4 non-fasted rats/sex were gavage-dosed daily for 14 days with Flubendiamide (NNI-0001), (14)C-labeled on the phthalic acid ring, radiochemical purity after purification of 99.2%, in an aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80. This study assessed ADME features including quantification of major metabolites. Rats were sacrificed either 9 hr, 24 hr, or 168 hr after the final (14th) dosing. Results from the present study should be compared to the primary single dose study (DPR Document No. 53013-0179, Record No. 226611). There was no substantial change in blood or plasma levels when comparing rats sampled 24 hr after 1, 6, or 13 daily doses. Distribution to tissues between 9 hr and 168 hr after repetitive dosing for 14 days found that label was moving through the g.i. tract more slowly in the present study than in the single-dose study during the first 24 hr. At 24 hours in the present study, much more of the label remained in the intestinal contents than was the case in the single-dose study. Also, tissue levels were not decreasing as rapidly in this study from 9 hr to 24 hr after dosing compared to the single dose study. By 7 days after dosing, tissue levels in the two studies were comparable. Overall absorption in the present study appeared to be markedly lower than was observed in the single dose study, based on percent of administered label found in the urine. This appears to reflect comparatively low absorption of a dose administered to non-fasted animals. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

通常，每组4只/性别的禁食大鼠一次通过灌胃给予氟苯二酰胺（NNI-0001），在酞酸环上或（在有限程度上）在苯胺环上标记（14）C，净化后的放射化学含量> 99.5%，在含有0.2% Tween 80的1%羧甲基纤维素钠水悬浮液中。本研究评估了ADME特征，包括在用2或200毫克/千克氟苯二酰胺处理后鉴定主要代谢物。标签在呼出的空气中的排泄量不大。超过90%的给药剂量通过粪便排出，与剂量或性别无关。尽管尿液是一个小途径（< 2%的给药剂量），但雄性在尿液中的标签传递始终高于雌性。高剂量水平导致显著降低吸收。两种标记形式的排泄模式和代谢物色谱图之间没有明显差异，这表明分子的大部分之间几乎没有裂解。血液和血浆的Tmax为6至12小时。标签的组织分布主要在大肠、肝脏和其他高灌注器官以及体脂中。低剂量治疗发现雄性组织的峰值水平比雌性高几倍。从9小时到24小时，雄性组织水平下降了大约90%，从24小时到168小时又下降了90%。然而，雌性没有像雄性那样迅速清除组织，因此168小时后雌性的残留组织浓度高于雄性。氟苯二酰胺上可供氧化的主要取代基是苯胺环上的甲基。最常见的产品是那个甲基碳的苄醇（指定为A-16）和苯甲酸（指定为A-18）。较少的中间物苯甲醛被指定为A-17。在代谢轮廓上出现了实质性的性别差异。在2 mg/kg雄性的粪便中，苄醇是主要的代谢物（占给药剂量的31-37%），其次是亲代氟苯二酰胺（占给药剂量的15-30%）和苯甲酸代谢物（占给药剂量的15-16%）。在2 mg/kg雌性的粪便中，66%的给药剂量是氟苯二酰胺，5-6%的给药剂量是苄醇，几乎没有苯甲酸代谢物。没有其他主要代谢物。在200 mg/kg的两种性别的粪便中，亲代氟苯二酰胺是主要的标记成分，表明吸收是可饱和的。雌性大鼠清除放射性的速度非常慢：对比2 mg/kg雄性在给药后9小时和168小时肝脏标签含量从5.628%下降到0.104%的给药剂量，而雌性在相同采样时间的含量为1.623%和1.305%的给药剂量。雌性大鼠对氟苯二酰胺的肝脏代谢能力有限，因此24小时内在雌性肝脏中明显积累了亲代氟苯二酰胺（比所有可提取代谢物组合的数量级多）。在雄性中，肝脏中几乎没有发现亲代氟苯二酰胺（不到苯甲醇或苯甲醛代谢物所代表剂量的半数）。雄性肝脏有较小但可测量的两种环结构之间裂解的唯一识别产物（苯胺片段）。

Typically sets of 4 fasted rats/sex were dosed once by gavage with Flubendiamide (NNI-0001), (14)C-labeled on either the phthalic acid ring or (to a limited extent) on the aniline ring, radiochemical content after purification > 99.5%, in an aqueous suspension of 1% sodium carboxymethylcellulose containing 0.2% Tween 80. This study assessed ADME features including identification of major metabolites following treatment with either 2 or 200 mg/kg flubendiamide. There was no significant excretion of label into expired air. Over 90% of administered dose was excreted in feces regardless of dose or sex. Although urine was a minor route (< 2% of administered dose), males consistently passed more label in urine than did females. High dose levels led to markedly reduced absorption. There was no obvious difference in excretion patterns and there were minimal differences in metabolite chromatograms between the two labeled forms, indicating that there was very little cleavage dividing major portions of the molecule. Tmax was 6 to 12 hours for blood and plasma. Tissue distribution of label was preferentially to the g.i. tract, liver and other highly perfused organs, and body fat. Low dose treatments found peak tissue levels in males several-fold higher than females. Tissue levels in males were lower by about 90% from 9 hrs to 24 hrs, and by another 90% from 24 hrs to 168 hrs. Females did not clear tissues as rapidly as males, however, so females had higher residual tissue concentrations at 168 hours than males. The primary substituent available for oxidation on flubendiamide is the methyl group on the aniline ring. The most common products were the benzyl alcohol (designated A-16) and the benzoic acid (designated A-18) of that methyl carbon. The less abundant intermediate benzaldehyde was designated as A-17. Substantial sex differences emerged in metabolic profiles. In the feces, the benzyl alcohol was the dominant metabolite in 2 mg/kg males (31-37% of administered dose), followed by parent flubendiamide (15-30% of administered dose), and the benzoic acid metabolite (15-16% of administered dose). In feces of 2 mg/kg females, 66% of administered dose was flubendiamide, 5-6% of administered dose was benzyl alcohol, and there was very little benzoic acid metabolite. There were no other major metabolites. Parent flubendiamide was the predominant labeled constituent in feces of both sexes at 200 mg/kg, indicating saturable absorption. Female rats were very slow to clear radioactivity: contrast liver label content in 2 mg/kg males dropping from 5.628% to 0.104% of administered dose at 9 hrs and 168 hrs after dosing vs. content in females of 1.623% and 1.305% of administered dose at the same sampling times. Female rats have limited hepatic metabolic capacity for flubendiamide, hence there was appreciable accumulation of parent flubendiamide in the livers of females at 24 hours (an order of magnitude more than all extractable metabolites combined). In males, very little parent flubendiamide was found in liver (less than half of the percent of dose represented by benzyl alcohol or benzaldehyde metabolites). Liver in males had smaller but measurable amounts of the sole identified product of cleavage between the two ring structures of flubendiamide (the aniline fragment).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

F-344 (F344/DuCrj) 大鼠和 Crlj: CD1 (ICR) 小鼠（每种类别、性别和给药期各4只）以200 mg/kg/天的剂量通过灌胃的方式给予未标记的氟虫酰胺，纯度为96.7%，载体为玉米油。治疗期为每天1次，持续1、7或14天。动物在最后一次给药后24小时被处死。研究者测定了血浆、肝脏和脂肪中氟虫酰胺及其碘磷酰亚胺代谢物（A-14）的浓度。在雄性动物中，这些组织中氟虫酰胺的浓度随时间并未增加。在雌性动物中，所有研究组织中有轻微的积累，到第7天达到稳态。A-14在两种性别的大鼠脂肪中似乎都有积累，到第7天达到稳态。氟虫酰胺在肝脏和脂肪中的浓度总是比血浆中高，而且雌性动物中的浓度远高于雄性。第7天，雄性大鼠肝脏和脂肪中氟虫酰胺的浓度分别为1.3和8.9 mg/kg。雌性大鼠肝脏和脂肪中的浓度分别为26.7和68.0 mg/kg。第7天，雄性和雌性大鼠肝脏和脂肪中A-14的浓度相同，分别为<1.0和2.9 mg/kg。第7天，雄性小鼠肝脏和脂肪中氟虫酰胺的浓度分别为2.3和3.4 mg/kg。雌性小鼠相应的水平为2.4和1.9 mg/kg（即与雌性大鼠明显积累的情况不同）。A-14在雄性和雌性小鼠中的水平通常低于定量限。这项研究表明，雌性大鼠对氟虫酰胺的有限代谢能力和倾向于代谢大量A-14的情况并不适用于小鼠的任何性别。

F-344 (F344/DuCrj) rats and Crlj: CD1 (ICR) mice (4/species/sex/dosing period) were dosed with 200 mg/kg/day unlabeled flubendiamide, purity 96.7% by gavage in corn oil. Treatments were daily for 1, 7, or 14 days. Animals were sacrificed 24 hr after the final dose. Investigators determined concentrations of flubendiamide and of the iodophthalimide metabolite (A-14) in plasma, liver, and fat. Flubendiamide did not increase in the in these tissues over time in males. There was a marginal accumulation in females in all studied tissues, reaching steady state by day 7. A-14 appeared to be accumulating in fat in rats of both sexes, reaching steady state by day 7. Flubendiamide was always more concentrated in liver and fat than in plasma, and concentrations were much higher in females than in males. Day 7 concentrations of flubendiamide in liver and fat of male rats at day 7 were 1.3 and 8.9 mg/kg, respectively. Liver and fat concentrations in female rats were 26.7 and 68.0 mg/kg. A-14 concentrations in male and female rats for liver and fat at day 7 were identical at < 1.0 and 2.9 mg/kg, respectively. Flubendiamide concentrations on day 7 in liver and fat of male mice were 2.3 and 3.4 mg/kg, respectively. Corresponding levels in female mice were 2.4 and 1.9 mg/kg (i.e. much unlike the marked accumulation in female rats). A-14 levels were generally below quantification limits in both male and female mice. This study indicates that limited metabolic capacity of female rats toward flubendiamide and tendency to metabolize significant amounts of A-14 do not apply to either sex of mice.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  1,3

制备方法与用途

理化性质

原药含量≥95.0%，纯品为白色结晶粉末，熔点在217.5～220.7℃之间。其蒸气压小于1×10⁻¹mPa（25℃），油水分配系数Kow lgP=4.2（20℃），相对密度1.659（20℃）。水中溶解度为29.9ug/L（20℃），在有机溶剂中的溶解度如下：对二甲苯0.488g/L，正庚烷0.000835g/L，甲醇26.0g/L，1,2-二氯乙烷8.12g/L，丙酮102g/L，乙酸乙酯29.4g/L。在pH 4~9的酸碱环境中稳定，在蒸馏水中5.5天（25℃）分解。

生物活性

氟苯虫酰胺对几乎所有鳞翅目害虫具有良好的活性，EC₅₀值均低于1.0mg(a.i./L)。其对小菜蛾成虫的EC₅₀为0.21mg(a.i./L)，与氯氟氰菊酯相当；对2龄幼虫的活性最高（EC₅₀为0.004mg(a.i./L)，是氯氟氰菊酯的60倍），但对卵无活性。实验表明，氟苯虫酰胺对斜纹夜蛾各龄期幼虫均有效，尤其1龄幼虫最敏感；与氯氟氰菊酯、灭多威、丙溴磷和多杀菌素相比，在防治5龄幼虫方面表现出显著优势。

为了更有效地防治害虫，在田间应用时应在幼虫期使用。

应用

氟苯虫酰胺通过控制肌肉中的钙离子释放来作用于鱼尼丁受体，这种全新的作用方式使其成为一种高效的杀虫剂。其主要代谢产物包括邻苯二甲酸、苯甲酸和苯甲醇等，在体内以粪便形式排出。

毒性

氟苯虫酰胺对雌雄大鼠急性经口LD₅₀ >2000mg/kg，皮肤接触LD₅₀ >2000mg/kg。对兔眼睛轻微刺激无害，对兔皮肤及豚鼠皮肤均无致敏作用；吸入LC₅₀ >0.0685 mg/L。长期研究显示雄大鼠NOEL为1.95 mg/(kg.d)，雌大鼠为2.40 mg/(kg.d)。ADI建议值为aRfD 0.995mg/kg，cRfD 0.024mg/kg（日本FSC）。

Ames试验结果呈阴性。

环境行为

氟苯虫酰胺在动物体内的吸收有限，主要通过粪便排出。代谢途径主要是利用甲基苯胺的多步氧化及葡萄糖醛酸化作用，谷胱甘肽结合邻苯二甲酸也是次要产物。

在土壤和水中，其主要代谢方式是光解。DT₅₀在水中的分解时间约为5.5天，在土壤中为11.6天。无氧条件下，在水中分解时间为365天，在土壤中为210~770天。氟苯虫酰胺及其代谢物的半衰期表明它们在连续使用后会在土壤和水中慢慢累积。

合成路线

氟苯虫酰胺主要通过以下中间体合成：3-碘邻苯二甲酸酐、2-甲基-2-氨基-1-(甲硫基)丙烷和2-甲基-4-(七氟异丙基)苯胺。具体合成步骤未详细列出，仅提及了重要的起始物料。

反应信息

• 作为反应物：
  描述：

  、 3-iodo-N'-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide 、 3-碘-N'-(2-甲磺酰基-1,1-二甲基乙烷基-N-{4-[1,2,2,2-四氟-1-(三氟甲基)乙基]-0-甲苯基}邻苯二酰胺 生成 邻苯二酰胺
  参考文献：
  名称：

  Silylated Carboxamides

  摘要：

  本发明涉及一种化合物的新型硅烷化羧酰胺，其化学式为（I），其中M，L，R1，R2，R3，R和A如描述中所定义，以及制备这些化合物的多种方法及其用于控制不需要的微生物的用途，还涉及新的中间体及其制备。

  公开号：

  US20070293455A1
• 作为产物：
  描述：

  3-iodo-N1-(2-methyl-4-heptafluoroisopropylphenyl)-N2-(1,1-dimethyl-2-methylsulfonylethyl)-1,2-benzene formamide 在 甲酸 、 硫酸 、 双氧水 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 3-碘-N'-(2-甲磺酰基-1,1-二甲基乙烷基-N-{4-[1,2,2,2-四氟-1-(三氟甲基)乙基]-0-甲苯基}邻苯二酰胺
  参考文献：
  名称：

  PROCESS FOR PRODUCING 2-HALOGENOBENZAMIDE COMPOUND

  摘要：

  公开号：

  EP1698619B1

文献信息

• [EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
  申请人：BASF SE

  公开号：WO2014206910A1

  公开（公告）日：2014-12-31

  The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式（I）中变量如索权和说明中所定义的自行车基取代异噻唑啉化合物。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种通过使用这些化合物来控制无脊椎动物害虫的方法，以及包含所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] AZOLINE COMPOUNDS<br/>[FR] COMPOSÉS AZOLINE
  申请人：BASF SE

  公开号：WO2015128358A1

  公开（公告）日：2015-09-03

  The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及式（I）的噁唑啉化合物，其中A、B1、B2、B3、G1、G2、X1、R1、R3a、R3b、Rg1和Rg2如权利要求和描述中所定义。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种利用这些化合物控制无脊椎动物害虫的方法，以及包括所述化合物的植物繁殖材料、农业和兽医组合物。
• [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。