在大鼠代谢研究中，将三唑啉酮-3-(14)C (MKH 3586，即氨甲酸唑)的水溶液以5.25至5.99毫克/千克的剂量单次灌胃给予4只雄性Fischer大鼠。给药后72小时内，放射性剂量的总体回收率为95%。大部分剂量在给药后24小时内通过尿液排出(64%的剂量)，表明吸收量很大。在给药后24小时内，通过粪便排出的剂量占27%。给药24小时后，只有2%的剂量通过排泄物回收。在给药后72小时，选定的组织中放射性浓度较低(0.004至0.073微克/克)。使用高效液相色谱(HPLC)和液相色谱-串联质谱(LC-MS/MS)分析，在大鼠排泄物中鉴定出了母体和9种代谢物。在排泄物中鉴定出的化合物占剂量的74%。在尿液(大约2%的剂量)和粪便(小于1%的剂量)中检测到少量的母体。排泄物中的主要代谢物是母体的羟基化、脱氨衍生物，即iPr-2-OH DA (34%的剂量)，主要在尿液中找到(32%的剂量)。还鉴定出了其他羟基化脱氨衍生物：tBu-OH DA (尿液中11%的剂量和粪便中4%的剂量)，以及iPr-1,2-di-OH DA (尿液中6%的剂量和粪便中小于1%的剂量)。母体的葡萄糖醛酸结合物，MKH 3586 GA，占剂量的11%，主要在粪便中(10%的剂量)。在排泄物中鉴定出的其他代谢物(每种小于或等于3%的剂量)包括：tBu-1,2-di-iPr-tri-OH DA；tBu-iPr-di-OH DA；iPr-1,3-diOH DA；tBu-OH-iPr-ene和DA。根据代谢轮廓，MKH 3586在雄性大鼠中的代谢主要涉及脱氨，随后是羟基化，并通过尿液排出。母体也发生葡萄糖醛酸结合并在粪便中排出。
In a rat metabolism study ... (triazolinone-3 (14)C) MKH 3586 (amicarbazone ... radiochemical purity > 99%) in water was admin to 4 male Fischer rats as a single gavage dose at 5.25 to 5.99 mg/kg ... Overall recovery of the radioactive dose was 95% by 72 hr following admin. The majority of the dose was recovered in the urine within 24 hr (64% dose), indicating substantial absorption. Fecal excretion accounted for 27% dose within 24 hr post-dose. Only 2% dose was recovered in the excreta after 24 hr ... Concn of radioactivity in the selected tissues at 72 hr post-dose were low (0.004 to 0.073 ug/g). HPLC and LC-MS/MS analysis were used to identify parent and 9 metabolites in excreta from male rats ... Identified cmpd in excreta accounted for 74% of the dose ... Minor amt of parent were detected in both urine (approximately 2% dose) and feces (< 1% dose). The major metabolite in excreta was a hydroxylated, deaminated derivative of the parent, iPr-2-OH DA (34% dose), mainly found in the urine (32% dose). Other hydroxylated deaminated derivatives were also identified: tBu-OH DA (11% dose in urine and 4% dose in feces), and iPr-1,2-di-OH DA (6% dose in urine and < 1% dose in feces). The glucuronic acid conjugate of the parent, MKH 3586 GA, accounted for 11% dose, mainly in the feces (10% dose). Other metabolites (each < or = 3% dose) identified in excreta included: tBu-1,2-di-iPr-tri-OH DA; tBu-iPr-di-OH DA; iPr-1,3-diOH DA; tBu-OH-iPr-ene and DA. Based on the metabolic profile, the metabolism of MKH 3586 in male rats primarily involves deamination followed by hydroxylation with elimination in the urine. Parent also undergoes glucuronic acid conjugation and elimination in the feces.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在大鼠代谢研究中...三唑啉酮-3-(14)C-4-甲基MKH 3586（氨基甲酸酯土壤代谢物...放射性纯度> 99%）的水溶液被单次灌胃给予4只雄性Fischer大鼠，剂量为4.86至5.22毫克/千克...放射性剂量的总体回收率为96小时后的91%。大部分剂量在12小时内通过尿液回收（70%剂量），总尿排泄占80%剂量，表明吸收量很大。粪便排泄（给药后0至24小时）占8%剂量。大约3%的剂量在24小时后在排泄物中回收...在给药后96小时，组织中的放射性浓度较低（0.002至0.028微克/克），每个组织的剂量< 0.1%。高效液相色谱、(1)H-核磁共振和液相色谱-串联质谱分析在排泄物中鉴定出12种成分...其中4种化合物以对映体对存在。鉴定的化合物占总剂量的75%...给药剂量的总体可追溯性约为82%...测试物质在尿液或粪便中未检出。土壤代谢物在异丙基基团上的羟基化形成了主要代谢物，4-甲基-i-Pr-2-OH DA MKH 3586（29%剂量），主要在尿液中找到（28%剂量）。在叔丁基团上的进一步羟基化导致4-甲基-t-Bu-iPr-2-二-OH DA MKH 3586的形成，占总剂量的12%。另外，异丙基基团的额外羟基化形成了4-甲基-iPr-1,2-二-OH DA MKH 3586，在尿液中的剂量占9%。母体的去甲基化形成了DA MKH 3586（<1%剂量），然后在异丙基基团上羟基化形成iPr-2-OH DA MKH 3586（8%剂量）。母体也可以在叔丁基团上羟基化形成4-甲基-tBu-OH DA MKH 3586（9%剂量），只在尿液中检测到。其他次要的鉴定代谢物是由于进一步的氧化，通常是羟基化。4-甲基DA MKH 3586在大鼠中的代谢途径主要涉及一系列的羟基化反应。没有检测到缀合物。/4-甲基MKH 3586（氨基甲酸酯土壤代谢物）/
In a rat metabolism study ... (triazolinone-3-(14)C) 4-methyl MKH 3586 (soil metabolite of amicarbazone ... radiochemical purity > 99%) in water was admin to 4 male Fischer rats as a single gavage dose at 4.86 to 5.22 mg/kg ... Overall recovery of the radioactive dose was 91% by 96 hr following admin. The majority of the dose was recovered in the urine within 12 hr (70% dose), with total urinary excretion accounted for 80% dose, indicating substantial absorption. Fecal excretion (0 to 24 hr post-dose) accounted for 8% dose. Approx 3% dose was recovered in the excreta after 24 hr ... At 96 hr post-dose, the concn of radioactivity in the tissues were low (0.002 to 0.028 ug/g), with < 0.1% dose in each tissue. HPLC, (1)H-NMR, and LC-MS/MS analysis identified 12 components in excreta ... 4 of these cmpd were present as chiral pairs. Identified cmpd accounted for 75% of the dose ... The overall accountability of the admin dose was ~ 82% ... The tested substance was not detected in the urine or feces. Hydroxylation of the soil metabolite at the isopropyl moiety formed the major metabolite, 4-Me-i-Pr-2-OH DA MKH 3586 (29% dose), which was found primarily in urine (28% dose). Further hydroxylation at the tertiary butyl group resulted in the formation of 4-Me-t-Bu-iPr-2-di-OH DA MKH 3586, which accounted for 12% dose. Alternatively, additional hydroxylation of isopropyl moiety formed 4-Me-iPr-1,2-di-OH DA MKH 3586, which constituted 9% dose in urine. Desmethylation of the parent formed DA MKH 3586 (<1% dose), which was then hydroxylated at the isopropyl moiety to form iPr-2-OH DA MKH 3586 (8% dose). The parent was also be hydroxylated at the tertiary butyl moiety to form 4-Me-tBu-OH DA MKH 3586 (9% dose), which was only detected in urine. The other minor identified metabolites occurred resulted from further oxidation, usually hydroxylation. The pathway for the metabolism of 4-methyl DA MKH 3586 in rats primarily involves a series of hydroxylation reaction. No conjugates were detected. /4-Methyl MKH 3586 (soil metabolite of amicarbazone)/
来源:Hazardous Substances Data Bank (HSDB)
代谢
... 植物和家畜中关注的残留物，用于容忍度和风险评估，包括 /amicarbazone（4-氨基-N-（1,1-二甲基乙基）-4,5-二氢-3-（1-甲基乙基）-5-氧代-1H-1,2,4-三唑-1-甲酰胺）/，一个脱氨代谢物 /（DA amicarbazone：N-（1,1-二甲基乙基）-4,5-二氢-3-（1-甲基乙基）-5-氧代-1H-1,2,4-三唑-1-甲酰胺）以及后者的一个羟基衍生物 /（iPr-2-OH DA amicarbazone：N-（1,1-二甲基乙基）-4,5-二氢-3-（1-羟基-1-甲基乙基）-5-氧代-1H-1,2,4-三唑-1-甲酰胺）。在饮用水评估中还包括脱氨代谢物的N-甲基衍生物 ...
... The residues of concern in plants and livestock for tolerances and risk assessment consist of /amicarbazone ( 4-Amino-N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazole-1-carboxamide)/, a desamino metabolite /(DA amicarbazone: N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazone-1-carboxamide), and a hydroxylated derivative of the latter /(iPr-2-OH DA amicarbazone: N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-hydroxyl-1-methylethyl)-5-oxo-1H-1,2,4-triazone-1-carboxamide). The desamino metabolite is also included in the drinking water assessment along with its N-methyl derivative ...
来源:Hazardous Substances Data Bank (HSDB)
代谢
提出了一个假设，玉米中的主要代谢途径涉及三唑氨基团的脱氨，形成去氨基代谢物（DA MKH 3586），然后在水合作用形成异丙基的次级碳上形成iPr-2-OH DA MKH 3586。其他途径包括异丙基甲基的水合作用形成iPr-1-OH DA MKH 3586，然后发生葡萄糖基化；叔丁基和异丙基的水合作用形成tBu-iPr-2-二OH DA MKH 3586。此外，DA MKH 3586形成了一种N-葡萄糖苷；羟基化的DA MKH 3586的葡萄糖基化形成了几种次要的O-葡萄糖苷。
/It was/ proposed that the major metabolic pathway in corn involves the deamination of the triazole amino group to form the desamino metabolite (DA MKH 3586) followed by hydroxylation at the tertiary carbon of the isopropyl group to form iPr-2-OH DA MKH 3586. Additional pathways involve hydroxylation of the isopropyl methyl to form iPr-1-OH DA MKH 3586, followed by glucosidation; hydroxylation of the t-butyl and isopropyl groups to form tBu-iPr-2-diOH DA MKH 3586. In addition, DA MKH 3586 formed an N-glucoside; and glucosidation of hydroxylated DA MKH 3586 formed several minor O-glucosides.
/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/
/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/
/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/
/LABORATORY ANIMALS: Acute Exposure/ Primary irritation indices /of amicarbazone/ in acute dermal tests were 0 in New Zealand white rabbits. /From table/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
进行了一项植物代谢研究，研究对象是玉米，土壤中施用了1.6倍于最大季节性施用率的(triazolinone-3-(14)C)amicarbazone；在温室中将玉米种子种植到容器中后，出土前4小时进行了土壤施用。玉米牧草、饲料和谷物中的总放射性残留物（TRRs）分别为0.988、2.369和0.054 ppm，收获前间隔（PHIs）为104至126天。总可提取残留物为91至100% TRR。残留物主要通过高效液相色谱（HPLC）分析进行表征/鉴定，通过薄层色谱（TLC）和液相色谱/质谱（LC/MS）进行确认分析。玉米商品中的总鉴定残留物为74至79%TRR。父本amicarbazone是牧草和饲料中鉴定出的主要残留物，在谷物中发现的量较小。谷物中鉴定出的主要残留物是代谢物iPr-2-OH DA MKH 3586，它也出现在牧草和饲料中。其他鉴定出的残留物包括DA MKH 3586、4-N-glu-DA MKH 3586和iPr-2-O-glu-DA MKH 3586在谷物、牧草和饲料中；以及仅在牧草中发现的tBu-iPr-2-diOH DA MKH 3586。在饲料中还鉴定出了另外四种葡萄糖/葡萄糖苷结合物，但数量较少（小于或等于5% TRR）。
A plant metabolism study was conducted on corn with soil application of (triazolinone-3-(14)C)amicarbazone at 1.6X the max seasonal rate; application to the soil was made pre-emergence, 4 hr after planting corn seed into containers in a greenhouse. The total radioactive residues (TRRs) were 0.988, 2.369, and 0.054 ppm in corn forage, fodder, and grain, respectively, with preharvest intervals (PHIs) of 104 to 126 days. Total extractable residues were 91 to 100% TRR. Residues were characterized/identified primarily by HPLC analysis with confirmatory analysis by TLC and LC/MS. Total identified residues were 74 to 79%TRR in corn commodities. Parent amicarbazone was the major residue identified in forage and fodder, and was found in smaller amt in grain. The major residue identified in grain was the metabolite iPr-2-OH DA MKH 3586, which was also found in forage and fodder. Other identified residues were DA MKH 3586, 4-N-glu-DA MKH 3586 and iPr-2-O-glu-DA MKH 3586 in grain, forage and fodder; and tBu-iPr-2-diOH DA MKH 3586 in forage only. Four additional glucose/glucoside conjugates were identified in small amt (< or = 5% TRR) in fodder.
... A 23 field corn field trials each consisted or 3 application scenarios - a single broadcast application made preemergence, a single preplant incorporated application (both at 0.45 lb ai/acre) and an early postemergence application (0.25 lb ai/acre). All applications were made using ground application equipment. Even though the early postemergence application rate was the lowest of the 3 applications, it resulted in the highest combined residues of amicarbazone and its metabolites DA MKH 3586 and iPr-2-OH DA MKH 3586; residues following preplant incorporated application were slightly higher than those following preemergence application. Combined residues were at most 0.56 ppm in forage, 0.43 ppm in stover, and approx 0.05 ppm in field corn grain.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
(三唑啉酮-3-(14)C)氨甲酰脲...通过口服给药给2只哺乳的山羊，饲料中的平均含量为101 ppm（是奶牛理论最大饲料负荷的42倍）。山羊每天给药一次，连续3天。在整个研究期间，每天收集两次牛奶，并在屠宰时收集组织（肌肉、脂肪、肝脏和肾脏）样本。放射性残留物在肝脏和肾脏的肉类副产品中最高，其次是肌肉、脂肪和牛奶...在山羊基质中鉴定的总残留物占到了91至99%的TRR。母体氨甲酰脲和代谢物DA氨甲酰脲是主要的残留物；氨甲酰脲在所有基质中都是主要的残留物，除了肾脏。代谢物iPr-2-OH DA氨甲酰脲在肾脏中是主要的残留物，但在所有其他基质中是次要的残留物。代谢物t-Bu-OH MKH 3586也在牛奶、肌肉和肾脏中被鉴定为主要残留物，但在脂肪和肝脏中是次要的残留物。代谢物iPr-Ene DA MKH 3586在肝脏中是主要的残留物，但在所有其他基质中是次要的残留物。其他鉴定的代谢物含量小于或等于9%的TRR；这些包括三唑啉酮MKH 3586、三唑啉酮DA MKH 3586、tBu-酸MKH 3586、tBu-iPr-2-二OH DA MKH 3586（仅在肾脏和肝脏中）、iPr-1,2-二OH DA MKH 3586和tBu-OH DA MKH 3586。
... (Triazolinone-3-(14)C)amicarbazone ... was admin orally to 2 lactating goats at an avg of 101 ppm in the diet (42x the max theoretical dietary burden to dairy cattle). The goats were dosed once per day for 3 consecutive days. Milk was collected twice daily throughout the study, and tissues (muscle, fat, liver, and kidney) were collected at sacrifice. Radioactive residues were highest in the meat by-products liver and kidney, followed by muscle, fat, and milk ... Total residues amounting to 91 to 99% TRR were identified in goat matrices. Both parent amicarbazone and metabolite DA amicarbazone were major residues; amicarbazone was a major residue in all matrices with the exception of kidney. Metabolite iPr-2-OH DA amicarbazone was a major residue in kidney but was a minor residue in all other matrices. Metabolite t-Bu-OH MKH 3586 was also identified as a major residue in milk, muscle, and kidney, but was a minor residue in fat and liver. Metabolite iPr-Ene DA MKH 3586 was a major residue in liver but was a minor residue in all other matrices. Other identified metabolites were found at < or = 9% TRR; these included triazolinone MKH 3586, triazolinone DA MKH 3586, tBu-Acid MKH 3586, tBu-iPr-2-diOH DA MKH 3586 (kidney and liver only), iPr-1,2-diOH DA MKH 3586, and tBu-OH DA MKH 3586.
... Encapsulated amicarbazone was admin orally to lactating cows for 30 days. Cows were dosed at 0.374, 1.238, or 4.538 ppm in the diet. Milk was sampled twice daily ... Samples of muscle, liver, kidney and fat were collected at sacrifice. Amicarbazone-related residues were below the method limit of quantitation (LOQ; <0.010 ppm) in whole milk samples collected over the course of the dosing period from the high-dose group ... Amicarbazone-related residues were highest in liver and kidney, and lower in muscle and fat. In the high dose group, residues were 1.165 to 1.193 ppm in liver, 0.080 to 0.127 ppm in kidney, 0.014 to 0.021 ppm in muscle, and < 0.010 to 0.012 ppm in fat ... Residues from the mid- and low-dose groups were 0.305 to 0.440 ppm and 0.191 to 0.235 ppm in liver, and 0.033 to 0.039 ppm and 0.017 to 0.018 ppm in kidney, respectively. Residues were below the method LOQ ... in muscle and fat samples from the mid-dose group ... The relationship between dosing level and amicarbazone-related residues appears to be linear in liver and kidney.
Degradation of amicarbazone herbicide by photochemical processes
摘要：
Amicarbazone is a triazolinone herbicide developed to replace atrazine in the world market. Several technologies have been studied aiming at removing pesticides from wastewater, seeking to study the degradation mechanisms involved and the degree of toxicity of the transformation products formed. In this context, our main goal was to study the degradation of amicarbazone in aqueous solution by direct photolysis, suggesting possible chemical structures for the transformation products according to a theoretical and fundamental approach. The effects of herbicide initial concentration, pH, dissolved oxygen and nitrate concentrations, the role of singlet oxygen, and the presence of propan-2-ol as a free radical scavenger in amicarbazone photodegradation are discussed for the first time. Among these variables, pH showed influence on the photochemical degradation pathway. For instance, the transformation product amicarbazole was obtained under mildly acidic conditions, while 4-amino-5-oxo-3-(propan-2-yl)-4,5dihydro-1H-1,2,4-triazole-1-carboxamide intermediate was found in both acidic and basic conditions. A primary degradation product formed as a result of deamination in acidic medium was found out. Concerning the effect of the variables involved in the process, the lowest AMZ half-life of 120 min was achieved under the following conditions: pH =3; [AMZ](0) = 50 mg L-1; 75W LP-Hg lamp. (C) 2013 Elsevier B.V.. All rights reserved.
[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.
[EN] 3-[(HYDRAZONO)METHYL]-N-(TETRAZOL-5-YL)-BENZAMIDE AND 3-[(HYDRAZONO)METHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE DERIVATIVES AS HERBICIDES<br/>[FR] DÉRIVÉS DE 3-[(HYDRAZONO))MÉTHYL]-N-(TÉTRAZOL-5-YL)-BENZAMIDE ET DE 3-[(HYDRAZONO)MÉTHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE UTILISÉS EN TANT QU'HERBICIDES
申请人：SYNGENTA CROP PROTECTION AG
公开号：WO2021013969A1
公开（公告）日：2021-01-28
The present invention related to compounds of Formula (I): or an agronomically acceptable salt thereof, wherein Q, R2, R3, R4, R5 and R6 are as described herein. The invention further relates to compositions comprising said compounds, to methods of controlling weeds using said compositions, and to the use of compounds of Formula (I) as a herbicide.
[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。
[EN] HERBICIDALLY ACTIVE HETEROARYL-S?BSTIT?TED CYCLIC DIONES OR DERIVATIVES THEREOF<br/>[FR] DIONES CYCLIQUES SUBSTITUÉES PAR HÉTÉROARYLE À ACTIVITÉ HERBICIDE OU DÉRIVÉS DE CELLES-CI
申请人：SYNGENTA LTD
公开号：WO2011012862A1
公开（公告）日：2011-02-03
The invention relates to a compound of formula (I), which is suitable for use as a herbicide wherein G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or latentiating group; Q is a unsubstituted or substituted C3-C8 saturated or mono-unsaturated heterocyclyl containing at least one heteroatom selected from O, N and S, or Q is heteroaryl or substituted heteroaryl; m is 1, 2 or 3; and Het is an optionally substituted monocyclic or bicyclic heteroaromatic ring; and wherein the compound is optionally an agronomically acceptable salt thereof.
The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
