吡唑醚菌酯 | 175013-18-0

• 物质功能分类: 化学农药原药 - 杀菌剂 - 其他杀菌剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 吡唑醚菌酯
• 中文别名: N-[2-[[1-(4-氯苯基)吡唑-3-基]氧甲基]苯基]-N-甲氧基氨基甲酸甲酯；百克敏；{2-[1-(4-氯苯基)-1H-吡唑-3-基氧甲基]苯基}甲氧基氨基甲酸甲酯；唑菌胺酯
• 英文名称: pyraclostrobin
• 英文别名: pyraclostrobine；methyl N-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]phenyl]-N-methoxycarbamate；methyl N-{2-[1-(4-chlorophenyl)-1H-pyrazol-3-yloxymethyl]phenyl}(N-methoxy)carbamate；methyl (2-(((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)methyl)phenyl)(methoxy)carbamate；pyrazole kresoxim；N‑[2‑[[1‑(4‑chlorophenyl)pyrazol‑3‑yl]oxymethyl]phenyl]‑N‑methoxycarbamate methyl ester
• CAS: 175013-18-0
• 化学式: C₁₉H₁₈ClN₃O₄
• 分子量: 387.823
• InChiKey: HZRSNVGNWUDEFX-UHFFFAOYSA-N

物化性质

• 熔点：
  63.7-65.2°
• 沸点：
  501.1±60.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：250 mg/mL（644.63 mM）
• LogP：
  4.250 (est)
• 颜色/状态：
  White or light beige crystalline solid
• 气味：
  Odorless[Health Canada; Regulatory Note: Pyraclostrobin-Headline EC-Cabrio EG (REG2003-06); Pest Management Regulatory Agency (2003)
• 蒸汽压力：
  1.95X10-10 mm Hg at 20 °C
• 碰撞截面：
  183.19 Ų [M+H]+ [CCS Type: TW]
• 保留指数：
  2967
• 稳定性/保质期：
  稳定性：纯品在水溶液中的光解半衰期为0.06天（约1.44小时）。

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  65.8
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

在毒代动力学研究中使用的动物的组织、排泄物和胆汁，以及额外给予单次剂量50 mg/kg bw/天的组（为了提供更多分析材料）中的代谢物被分析了吡咯克酸的含量。为了确定血浆、肝脏和肾脏中的代谢物，额外组使用单次剂量的14C-甲苯基-或14C-氯酚环标记的吡咯克酸5和50 mg/kg bw，并在8小时后牺牲。使用高效液相色谱（HPLC）、液相色谱-质谱（LC-MS）和核磁共振（NMR）鉴定代谢物。吡咯克酸的代谢主要通过三条主要途径，主要涉及对吡咯克酸分子的三个主要部分的改变。甲氧基在甲苯基甲氧基碳酰胺部分容易丢失，很少有主要代谢物保留这个群体。芳香环和/或吡唑环的羟基化随后是葡萄糖苷酸和偶尔硫酸结合，许多代谢物来自氯酚-吡唑或甲苯基甲氧基碳酰胺部分，在醚键断裂后，随后是环羟基化和葡萄糖苷酸或硫酸结合。代谢物在两性和所有剂量下都是相似的。胆汁或尿液中没有发现未改变的母化合物，只在粪便中发现了少量。从尿液中回收的鉴定代谢物占主导地位的化合物有：环羟基化的吡咯克酸；氯酚吡唑部分在吡唑环上羟基化，有无硫酸结合；甲苯基甲氧基碳酰胺部分的葡萄糖苷酸；甲苯基甲氧基碳酰胺部分的苯甲酸衍生物。在粪便中，主要的代谢物是去甲氧基化和吡唑环羟基化的吡咯克酸。在胆汁中，主要的代谢物是吡咯克酸在吡唑环4'位置的羟基化葡萄糖苷酸，这个化合物和粪便中发现的去甲氧基衍生物也是从血浆和肝脏中分离出的主要代谢物。甲氧基碳酰胺部分的去甲氧基化似乎主要发生在肠道，因为胆汁中的主要代谢物保留了这一群体，而在粪便中主要的代谢物是去甲氧基衍生物。从肾脏中分离出的放射性标记大部分是以未改变的母化合物和去甲氧基衍生物的形式存在。

Tissues, excreta and bile from animals used in the toxicokinetics studies and from additional groups given a single dose at 50 mg/kg bw per day (to provide more material for analysis) were analysed for metabolites of pyraclostrobin. In order to determine the metabolites in the plasma, liver and kidneys, additional groups were treated with a single dose of 14C-tolyl- or 14C-chlorophenol ring-labelled pyraclostrobin at 5 and 50 mg/kg bw and sacrificed 8 hr later. Metabolites were identified using high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). The metabolism of pyraclostrobin proceeded through three main pathways primarily involving alterations to the three major portions of the pyraclostrobin molecule. The methoxy group on the tolyl-methoxycarbamate moiety was readily lost, with few major metabolites retaining this group. Hydroxylation of the aromatic and/or pyrazole rings was followed by glucuronide and occasionally sulfate conjugation, and many metabolites were derived from the chlorophenol-pyrazole or tolyl-methoxycarbamate moieties of pyraclostrobin, following cleavage of the ether linkage, with subsequent ring hydroxylation and glucuronide or sulfate conjugation. Metabolites were similar in both sexes and at all doses. No unchanged parent compound was found in the bile or urine and only small amounts in the faeces. Compounds dominating the identified metabolites recovered from the urine were: ring-hydroxylated pyraclostrobin; the chlorophenol pyrazole moiety hydroxylated on the pyrazole ring with or without a sulfate conjugate; a glucuronide of the tolyl-methoxycarbamate moiety; and a benzoic acid derivative of the tolyl-methoxycarbamate moiety. In the feces, the dominant metabolite was a demethoxylated and pyrazole ring hydroxylated pyraclostrobin. In the bile, the primary metabolite was a glucuronide of pyraclostrobin hydroxylated on the pyrazole ring at the 4' position and this compound, together with the demethoxylated derivative found in the faeces, was also the dominant metabolite isolated from the plasma and the liver. Demethoxylation of the methoxycarbamate moiety appeared to occur primarily in the gut, as the major metabolite in the bile retains this group intact whereas in the feces the major metabolite is the demethoxylated derivative. Most of the radiolabel isolated from the kidneys was in the form of the unchanged parent compound and a demethoxylated derivative.

来源:Hazardous Substances Data Bank (HSDB)

代谢

维斯特大鼠被给予氯苯基标记的吡咯克司特罗宾（>98%化学纯度，>98%放射化学纯度）或甲苯基标记的吡咯克司特罗宾（>98%化学纯度，>98%放射化学纯度），并用未标记的吡咯克司特罗宾（BAS 500 F）调整至所需剂量，纯度为99.8%。...在给药后8小时收集组织样本，以达到最大组织水平以进行分析。数据没有显示性别差异。剂量水平（5或50毫克/千克）和治疗历史（每天50毫克/千克吡咯克司特罗宾预处理2周）对代谢处置没有明显影响。最丰富的粪便代谢物是500M08（去甲氧基的ai，吡唑环4位被羟基化），占总给药剂量的约38%。其他显著的粪便代谢物进一步被羟基化：通常是在氯苯环上，有时也在甲苯环上。主要的胆汁代谢物是500M46（由ai的吡唑环碳4位的羟基化随后与葡萄糖醛酸结合形成）。大多数较小的胆汁代谢物也是葡萄糖醛酸苷。没有一个尿液代谢物超过给药剂量的约3%。主要的尿液代谢物是各种裂解醚氧（常形成葡萄糖醛酸或苯甲酸衍生物）的产品，或者是500M06（去甲氧基的500M46）。可检测到的血浆残留物仅限于500M06和500M46（约占给药剂量的0.02%）。这些代谢物加上母体吡咯克司特罗宾在肝脏中含量更高（这3种残留物合计约占剂量的0.5%）。只有吡咯克司特罗宾可以在肾脏中检测到，约占剂量的0.03%。因此，吸收的吡咯克司特罗宾被有效地代谢为极性产物，并有效地从体内清除。

Wistar rats were dosed ... with chlorophenyl-labeled pyraclostrobin (>98% chemical purity, >98% radiochemical purity) or tolyl-labeled pyraclostrobin (>98% chemical purity, >98% radiochemical purity), adjusted with unlabeled pyraclostrobin (BAS 500 F), 99.8 % purity to desired dose. ... Tissue samples were collected 8 hr after dosing, to achieve maximal tissue levels for analysis. Data did not demonstrate sex differences. Dose levels (5 or 50 mg/kg) and treatment history (2 week pre-treatment with 50 mg/kg/day pyraclostrobin) had no apparent effect on metabolic disposition. The most abundant fecal metabolite was 500M08 (de-methoxylated ai, which is hydroxylated in the 4-position of the pyrazole ring), accounting for about 38% of total administered dose. Other significant fecal metabolites were further hydroxylated: usually on the chlorophenyl ring and sometimes also on the tolyl ring. The major biliary metabolite was 500M46 (formed by hydroxylation followed by glucuronidation of carbon 4 of the pyrazole group of the ai). The majority of lesser biliary metabolites were also glucuronides. No single urinary metabolite comprised more than about 3% of administered dose. Predominant urinary metabolites were various products of cleavage of the ether oxygen (often to form a glucuronide or benzoic acid derivative), or 500M06 (de-methoxylated 500M46). Detectable plasma residues were limited to 500M06 and 500M46 (representing about 0.02% of administered dose). These metabolites plus parent pyraclostrobin were found in liver in higher amounts (these 3 residues combined representing about 0.5% of dose). Only pyraclostrobin could be detected in kidneys, to the extent of about 0.03% of dose. Thus absorbed pyraclostrobin is efficiently metabolized to polar products and is cleared effectively from the body.

来源:Hazardous Substances Data Bank (HSDB)

代谢

代谢物是甲基-N-(((1-(4-氯苯基)吡唑-3-基)氧基]甲基)碳酰胺（BF 500-3）

Metabolite /is/ methyl-N-(((1- (4-chlorophenyl) pyrazol-3-yl)oxy]otolyl) carbamate (BF 500-3)

来源:Hazardous Substances Data Bank (HSDB)

代谢

代谢的主要途径涉及吡唑环和其他环系统的去甲氧基化和羟基化，随后进行葡萄糖醛酸化。

Major routes of metabolism involved demethoxylation and hydroxylation of the pyrazole and other ring systems followed by glucuronidation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：数据不足以评估人类致癌潜力

Cancer Classification: Data are Inadequate for an Assessment of Human Carcinogenic Potential

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 毒性数据

大鼠LC50 > 310 mg/m³/4小时 < 1,070 mg/m³/4小时

LC50 (rat) > 310 mg/m3/4h < 1,070 mg/m3/4h

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 人类毒性摘录

吞咽可能致命。对眼睛造成严重但暂时性的伤害。对皮肤有刺激性。如果通过皮肤吸收，有害。/标题/

/SIGNS AND SYMPTOMS/ May be fatal if swallowed. Causes substantial but temporaly eye injury. Causes skin irritation. Harmful if absorbed through skin. /Headline/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给药。在给雄性和雌性Wistar大鼠（至少7周龄）口服给药碳-14标记的吡唑菌胺（纯度>98%）后，研究了吡唑菌胺的吸收、分布和消除。在一系列四个实验中，研究了在给药后6、12和24小时以及此后每隔24小时直至168小时或直到90%的放射性物质被排泄时吡唑菌胺的排泄情况。在前三个实验中，每组四只雄性和四只雌性大鼠口服给予14C-甲苯基-或14C-氯苯基-标记的吡唑菌胺或未标记的吡唑菌胺，剂量为50毫克/千克体重。在第四个实验中，每组四只雄性和四只雌性大鼠口服给予14C-甲苯基-标记的吡唑菌胺，剂量为5毫克/千克体重。在每次实验结束时，处死动物并检测心脏、肝脏、脾脏、骨骼、皮肤、肺、卵巢、骨髓、尸体、肌肉、肾脏、睾丸、大脑、胰腺、子宫、脂肪组织、胃及其内容物、甲状腺、肾上腺、血液/血浆和肠道及其内容物中的放射性。在两个使用标记吡唑菌胺的实验中，从每组的两只雄性大鼠中收集呼出的空气，以确定14C-标记气体的呼出情况。另外进行了两个实验，以研究在给予5或50毫克/千克体重的14C-甲苯基-标记吡唑菌胺后血液中放射性浓度的变化。在给药后0.5、1、2、4、8、24、48、72、96和120小时，从动物中采集血液样本（100-200微升），并检测全血和血浆中的放射性物质含量。在5毫克/千克体重给药后0.5、8、20和42小时，以及50毫克/千克体重给药后0.5、24、36和72小时，检测了处死动物的组织分布。为了研究吡唑菌胺的胆汁排泄，将动物的胆管插管并收集胆汁，直至在给予5或50毫克/千克体重的14C-甲苯基-标记吡唑菌胺后48小时，每隔3小时收集一次（持续时间取决于动物的健康状况和后期时间点的排泄率）。在给予14C-甲苯基-标记吡唑菌胺5或50毫克/千克体重的单次剂量后，血浆中放射性物质的浓度最初在0.5到1小时达到峰值；在5或50毫克/千克体重的雄性和5毫克/千克体重的雌性中，8小时后出现第二次峰值，在50毫克/千克体重的雌性中，24小时后出现第二次峰值。由于在8到24小时之间没有采样点，因此给予高剂量的雌性达到峰值的时间差异很可能是至少部分人为的。在第二次峰值之后，血浆浓度在120小时后降至<0.1微克当量/克。终末半衰期在男性和女性中相似，但在5毫克/千克体重时比50毫克/千克体重时长50%。血浆浓度-时间曲线下面积大致与剂量成正比，表明在高剂量下吸收未达到饱和。

Oral administration. The absorption, distribution, and elimination of pyraclostrobin were studied in male and female Wistar rats (aged at least 7 weeks) after oral administration of pyraclostrobin (purity, >98%) radiolabelled with carbon-14 at either the tolyl or chlorophenyl rings. ... In a series of four experiments, the excretion of pyraclostrobin was studied in excreta collected at 6, 12 and 24 hr after dosing, and at 24 hr intervals thereafter for 168 hr, or until 90% of the applied radioactivity had been excreted. In the first three experiments, groups of four male and four female rats were given a single oral dose of 14C-tolyl- or 14C-chlorophenyl-labelled pyraclostrobin or unlabelled pyraclostrobin at 50 mg/kg bw. In the fourth experiment, four rats of each sex were given a single oral dose of 14C-tolyl-labelled pyraclostrobin at 5 mg/kg bw. At the end of each of these experiments, the animals were sacrificed and the heart, liver, spleen, bone, skin, lung, ovaries, bone marrow, carcass, muscle, kidney, testes, brain, pancreas, uterus, adipose tissue, stomach and contents, thyroid glands, adrenal glands, blood/plasma and intestinal tract and contents were assessed for radioactivity. Exhaled air was also collected from two males in each of the two experiments using radiolabelled pyraclostrobin in order to determine exhalation of 14C-labelled gases. Two additional experiments were conducted to examine blood concentrations of radioactivity after administration of 14C-tolyl-labelled pyraclostrobin at 5 or 50 mg/kg bw. Blood samples (100-200 uL) were taken from animals at 0.5, 1, 2, 4, 8, 24, 48, 72, 96 and 120 hr after dosing, and the amount of radioactivity in whole blood and plasma was assessed. Tissue distribution was examined in animals sacrificed at 0.5, 8, 20 and 42 hr after dosing at 5 mg/kg bw, and at 0.5, 24, 36 and 72 hr after dosing at 50 mg/kg bw. The heart, liver, spleen, bone, skin, lung, ovaries, bone marrow, carcass, muscle, kidney, testes, brain, pancreas, uterus, adipose tissue, stomach and contents, thyroid glands, adrenal glands, blood/plasma and intestinal tract and contents were assessed for radioactivity. To examine biliary excretion of pyraclostrobin, bile ducts of the animals were cannulated and bile was collected at 3 hr intervals until 48 hr after administration of 14C-tolyl-labelled pyraclostrobin at 5 or 50 mg/kg bw in four animals of each sex at each dose (the duration depended on the health of the animals and the excretion rate at later time-points). In rats given a single dose of 14C-tolyl-labelled pyraclostrobin at either 5 or 50 mg/kg bw, plasma concentrations of radioactivity initially peaked after 0.5 to 1 hr; there was a secondary peak after 8 hr in males at 5 or 50 mg/kg bw and females given 5 mg/kg bw, and after 24 hR in females given 50 mg/kg bw. The magnitude of the difference in the time to peak for females, given the high dose, is likely to be at least partially artifactual owing to the absence of a sampling point between 8 and 24 hr. After the second peak, plasma concentrations declined to <0.1 ug equivalent/g after 120 hr. The terminal half-lives were similar in males and females, but were 50% longer at 5 mg/kg bw than at 50 mg/kg bw. The area under the curve of plasma concentration-time was approximately proportional to dose for each sex, indicating that absorption was not saturated at the higher dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠单次口服剂量为50毫克/千克体重的14C-甲苯标记的戊唑醇后，0.5小时内，放射性活性的最高浓度出现在消化道（肠道28至39微克当量/克；肠道内容物63至92微克当量/克；胃325至613微克当量/克；胃内容物1273至1696微克当量/克）。肝脏（13至25微克当量/克）的放射性活性浓度高于肾脏（4至7微克当量/克）和血浆（2至6微克当量/克），最低值记录在骨骼（0.1至0.3微克当量/克）和大脑（1至2微克当量/克）中。72小时后，组织和器官的含放射性活性小于2.6微克当量/克。在5毫克/千克体重的剂量下，0.5小时后，放射性活性的最高浓度也出现在消化道（肠道5微克当量/克；肠道内容物7至9微克当量/克；胃49至89微克当量/克；胃内容物160至205微克当量/克）。42小时后，组织和器官的含放射性活性小于0.7微克当量/克。在大鼠预先用未标记的戊唑醇处理14天，并给予单次口服剂量为5毫克/千克体重的14C-甲苯标记的戊唑醇后，120小时内在甲状腺（0.18至0.35微克当量/克）和肝脏（0.1微克当量/克）中发现了放射性活性的最高浓度。在其他所有组织中，记录的放射性活性浓度小于0.1微克当量/克。戊唑醇的快速且基本完全的排泄以及在整个观察期间组织浓度的降低，表明其积累的潜力较低。

After a single oral dose of 14C-tolyl-labelled pyraclostrobin at 50 mg/kg bw, the highest concentrations of radioactivity /in rats/ were found in the gastrointestinal tract (gut, 28 to 39 ug equivalent/g; gut contents, 63 to 92 ug equivalent/g; stomach, 325 to 613 ug equivalent/g; stomach contents, 1273 to 1696 ug equivalent/g) after 0.5 hr. The liver (13 to 25 ug equivalent/g) had higher concentrations of radioactivity than the kidneys (4 to 7 ug equivalent/g) and plasma (2 to 6 ug equivalent/g), with lowest values being recorded in the bone (0.1 to 0.3 ug equivalent/g) and brain (1 to 2 ug equivalent/g). After 72 hr, tissues and organs contained <2.6 ug equivalent/g. After a dose of 5 mg/kg bw, the highest concentrations of radioactivity were also found in the gastrointestinal tract (gut, 5 ug equivalent/g; gut contents, 7 to 9 ug equivalent/g; stomach, 49 to 89 ug equivalent/g; stomach contents, 160 to 205 ug equivalent/g) after 0.5 hr. After 42 hr, tissues and organs contained <0.7 ug equivalent/g. In rats that were pretreated with unlabelled pyraclostrobin for 14 days and given a single oral dose of 14C-tolyl-labelled pyraclostrobin at 5 mg/kg bw, the highest concentrations of radioactivity after 120 hr were found in the thyroid gland (0.18 to 0.35 ug equivalent/g) and the liver (0.1 ug equivalent/g). In all other tissues, the concentration of radioactivity recorded was <0.1 ug equivalent/g. The rapid and essentially complete excretion of pyraclostrobin and the decline of tissue concentrations to low levels over the observation period, suggests a low potential for accumulation.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠的四项口服实验中，放射活性的总体回收率为91%至105%。在单次口服给予14C-甲苯基标记的吡咯菌素5或50毫克/千克体重后的前48小时内，大约10%至13%的给药放射活性通过尿液排出，74%至91%通过粪便排出。在120小时后，通过尿液排出的放射活性总量为11%至15%，通过粪便排出的为81%至92%。在接受14天未标记吡咯菌素预处理后，再给予5毫克/千克体重的14C-甲苯基标记的吡咯菌素单次口服的大鼠中，也观察到了类似的排泄模式（48小时后尿液中为12%至13%，粪便中为76%至77%；120小时后尿液中为12%至14%，粪便中为79%至81%），以及给予50毫克/千克体重的氯苯基标记的吡咯菌素单次口服的大鼠（48小时后尿液中为11%至15%，粪便中为68%至85%；120小时后尿液中为12%至16%，粪便中为74%至89%）。在用50毫克/千克体重的14C-甲苯基或14C-氯苯基标记的吡咯菌素处理的大鼠中，呼出的空气中没有检测到放射性。在组织和器官中，120小时后剩余的放射性在50毫克/千克体重时小于1毫克当量/克，在5毫克/千克体重时小于0.1毫克当量/克。在给予5或50毫克/千克体重的14C-甲苯基标记的吡咯菌素后48小时内，约35%至38%的给药放射活性通过胆汁排出，结合对尿液排出的观察，表明大约50%的给药剂量已被吸收。

The overall recovery of radioactivity was 91 to 105% in all /four oral experiments in rats/. In the first 48 hr after a single oral dose of 14C-tolyl-labelled pyraclostrobin at 5 or 50 mg/kg bw, 10 to 13% of the administered radioactivity was excreted in the urine and 74 to 91% was excreted in the feces. The total amount of radioactivity excreted in the urine and feces after 120 hr was 11 to 15% and 81 to 92%, respectively. A similar pattern of excretion was observed in rats that were pre-treated with unlabelled pyraclostrobin for 14 days and given a single oral dose of 14C-tolyl-labelled pyraclostrobin at 5 mg/kg bw of (12 to 13% in the urine and 76 to 77% in the feces after 48 hr; 12 to 14% in the urine and 79 to 81% in the feces after 120 hr) and in rats given a single oral dose of chlorophenyl-labelled pyraclostrobin at 50 mg/kg bw (11 to 15% in the urine and 68 to 85% in the feces after 48 hr; 12 to 16% in the urine and 74 to 89% in the feces after 120 hr). There was no detectable radioactivity in the expired air from rats treated with 14C-tolyl- or 14C-chlorophenyl-labelled pyraclostrobin at 50 mg/kg bw. In tissues and organs, the radioactivity that remained after 120 hr was <1 mg equivalent/g at 50 mg/kg bw and <0.1 mg equivalent/g at 5 mg/kg bw. Within 48 hr after administration of 14C-tolyl-labelled pyraclostrobin at 5 or 50 mg/kg bw of, 35 to 38% of the administered radioactivity was excreted via the bile, indicating, in conjunction with observations on urinary excretion, that approximately 50% of the administered dose had been absorbed.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

皮肤给药。在给16只雄性Wistar大鼠单次皮肤给药14C标记的吡唑嘧菌灵（在Solvesso中）后，评估了其吸收、分布和排泄，给药剂量为0.015、0.075或0.375 mg/cm2，相当于0.15、0.75和3.75 mg/动物，或者大约为0.8、4和18 mg/kg bw。动物接触试验物质4小时（每组4只大鼠）或8小时（每组12只大鼠），并在暴露开始后4、8、24或72小时每组处死4只大鼠。在给药前24小时，将肩部约10 cm2的区域剃毛并用丙酮清洗。将硅酮环粘在皮肤上，并用注射器给药（10 uL/cm2），在给药前后称重。然后在硅酮环表面粘上尼龙网，并用多孔绷带覆盖。暴露期结束后，移除保护套，用肥皂溶液清洗暴露的皮肤。处死后，评估排泄物、血细胞、血浆、肝脏、肾脏、尸体、治疗和未治疗的皮肤中的放射性浓度。还评估了笼子、皮肤清洗和保护套，包括硅酮环中的放射性。在所有组中，回收了99到110%的放射性。在8小时暴露后的72小时处死时，吸收了1.6到2.6%的给药剂量，22到26%在皮肤或皮肤清洗中，72到80%在保护套上回收。只有0.2到0.4%和0.9到1.8%分别通过尿液和粪便排出。

Dermal application. The absorption and, to a limited extent, the distribution and excretion of 14C-labelled pyraclostrobin (in Solvesso) in groups of 16 male Wistar rats was assessed after a single dermal application at a nominal dose of 0.015, 0.075 or 0.375 mg/cm2, corresponding to 0.15, 0.75 and 3.75 mg/animal or approximately 0.8, 4 and 18 mg/kg bw. Animals were exposed to the test material for 4 (four rats per group) or 8 (12 rats per group) hr and four rats per group were sacrificed at 4, 8, 24 or 72 hr after the start of the exposure. An area of approximately 10 cm2 on the shoulders was clipped free of hair and was washed with acetone 24 hr before dosing. A silicone ring was glued to the skin and the test substance preparation (10 uL/cm2) was administered with a syringe, which was weighed before and after application. A nylon mesh was then glued to the surface of the silicone ring and covered with a porous bandage. After the exposure period, the protective covers were removed and the exposed skin was washed with a soap solution. After sacrifice, the concentration of radioactivity in the excreta, blood cells, plasma, liver, kidneys, carcass, treated and untreated skin was assessed. Radioactivity in the cage and skin wash and the protective covering, including the silicone ring, was also assessed. In all groups, 99 to 110% of the radioactivity was recovered. At sacrifice at 72 hr, after an 8 hr exposure, 1.6 to 2.6% of the administered dose was absorbed, 22 to 26% was on the skin or in the skin wash, and 72 to 80% was recovered on the protective cover. Only 0.2 to 0.4% and 0.9 to1.8% was excreted in the urine and faeces, respectively.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  N
• 安全说明：
  S60,S61
• 危险类别码：
  R50/53
• WGK Germany：
  2
• 危险品运输编号：
  UN 3077 9/PG 3
• 储存条件：
  制剂在常温下储存于20°C至25°C范围内可确保其稳定性长达2年。

制备方法与用途

应用

适宜作物包括小麦、水稻、花生、葡萄、蔬菜、香蕉、柠檬、咖啡、果树、核桃、茶树、烟草和观赏植物、草坪及其他大田作物。

对作物安全性：该化合物不仅毒性低，对非靶标生物安全，而且对使用者和环境均安全友好。在推荐使用剂量下，绝大部分试验结果表明对作物无药害，但对极个别美洲葡萄和梅品种在某一生长期有药害。

防治对象：由子囊菌纲、担子菌纲、半知菌类和卵菌纲真菌引起的作物病害。

使用方法：主要用于茎叶喷雾。推荐使用剂量为：

• 作物：50～250 g (a.i.) / hm²
• 草坪：280～560 g (a.i.) / hm²

杀菌剂—百克敏（pyraclostrobin）

又称吡唑醚菌酯、唑菌胺酯，为甲氧基丙烯酸酯类广谱杀菌剂。其作用机理是通过抑制线粒体呼吸来杀灭病原真菌，具有保护、治疗和根治作用。1993年巴斯夫公司发现的含吡唑结构的strobin类杀菌剂，2002年上市。它高效、广谱、低毒，且对环境安全友好。至今，该有效成分已在60多个国家的150多种作物上登记使用。

作用机制

百克敏通过阻止细胞色素b和 c,间电子传递而抑制线粒体呼吸作用，使线粒体不能产生和提供细胞正常代谢所需要的能量(ATP)，最终导致细胞死亡。它具有较强的抑制病菌孢子萌发能力，对叶片内菌丝生长有很好的抑制作用，并且持效期较长。该化合物在植物体内传导性好，在茎叶表面形成保护膜。

安全性

无潜在诱变性，对兔、大鼠无潜在致畸性和致癌性，对大鼠繁殖无不良影响。ADI值为0.03 mg/kg。

抗药性的风险

在中国，吡唑醚菌酯的风险主要在于抗药性的风险，且比国外更大。目前在全世界范围内，吡唑醚菌酯的抗性普遍发生，国内企业在产品配方及用药次数上的忽略以及农民滥用药加速了抗性的发生。随着大量使用，可以预见的是抗药性群体和病害种类将会快速上升。中国缺乏杀菌剂抗药性管理措施，一旦大面积发生将无法控制。

解决抗性的一个主要方法是运用预混的混剂方式推向市场。巴斯夫预混剂成分包括代森联、烯酰吗啉、啶酰菌胺、氟环唑、氟唑菌酰胺、二氰蒽醌、叶菌唑和灭菌唑等，通过混配可以延长化合物生命周期并扩大应用范围。

生物活性

百克敏（Pyraclostrobin）是一种球果苷杀菌剂，可抑制真菌和哺乳动物细胞的线粒体复合物 III (mitochondrial complex III)，诱导3T3-L1 细胞内甘油三酯的积累。

反应信息

• 作为反应物：
  描述：

  吡唑醚菌酯 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以92%的产率得到N-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]phenyl]-N-methoxycarbamic acid
  参考文献：
  名称：

  一类含三苯基鏻阳离子的甲氧基丙烯酸酯类化合物及合成方法与应用

  摘要：

  本发明公开了属于农用杀菌剂制备技术领域，特别涉及一类含三苯基鏻阳离子的甲氧基丙烯酸酯类化合物及合成方法与应用，给出了化合物的结构通式I及其合成路线；并用化合物中活性成分制成的病菌防治剂在农作物、园艺和蔬菜中的应用；该病菌防治剂对农作物上病菌引起的病害具有很好的防治作用；特别是这些病菌防治剂的活性高，在很低的剂量就表现出非常好的防效，并有广泛的防治谱。

  公开号：

  CN110105389A
• 作为产物：
  描述：

  甲基硝基苯 在 正丙胺 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 碳酸氢钠 、 potassium carbonate 、 氯化铵 、 锌 作用下， 以 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 7.0h， 生成 吡唑醚菌酯
  参考文献：
  名称：

  一种吡唑醚菌酯的合成工艺

  摘要：

  本发明提供一种吡唑醚菌酯的合成工艺，可分成五个步骤：(1)邻硝基甲苯与NH4Cl在锌粉及合金微纳米粉体的催化作用下发生还原反应；(2)羟胺的酰化反应；(3)甲基化反应；(4)通过溴化反应得到N‑甲氧基‑N‑2‑溴甲基苯基氨基甲酸甲酯；(5)用DMF作为溶剂溶解N‑甲氧基‑N‑2‑溴甲基苯基氨基甲酸甲酯配成溶液后备用，将1‑(4‑氯苯基)‑吡唑醇、K2CO3、丙酮一起放入反应器中，升温回流后，向反应器内缓慢滴加N‑甲氧基‑N‑2‑溴甲基苯基氨基甲酸甲酯溶液，回流反应结束后得到产物吡唑醚菌酯。与现有技术相比，本发明的制备方法简单，原材料价廉易得，反应条件温和，得到的目标产物纯度和收率高。

  公开号：

  CN106008347A
• 作为试剂：
  描述：

  [4-Bromo-3-[(5-bromopyrimidin-4-yl)methoxy]phenyl]methoxy-tert-butyl-dimethylsilane 在 吡唑醚菌酯 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四丁基氟化铵 、 potassium acetate 、 镍 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 methyl 7-(((S)-1-((2S,4R)-2-(((5H-chromeno[3,4-d]pyrimidin-8-yl)methyl)formamido)-4-hydroxypyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-7-oxoheptanoate
  参考文献：
  名称：

  WO2024067818A1

  摘要：

  公开号：

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] 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] SUBSTITUTED QUINAZOLINES AS FUNGICIDES<br/>[FR] QUINAZOLINES SUBSTITUÉES, UTILISÉES EN TANT QUE FONGICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2010136475A1

  公开（公告）日：2010-12-02

  The present invention relates to a compound of formula (I) wherein wherein the substituents have the definitions as defined in claim 1or a salt or a N-oxide thereof, their use and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.

  本发明涉及一种具有如下式（I）的化合物，其中取代基具有权利要求1中定义的定义，或其盐或N-氧化物，它们的用途以及用于控制和/或预防植物中微生物感染，特别是真菌感染的方法，以及制备这些化合物的方法。
• [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。