2-[(Z)-N-[(3,5-difluorophenyl)carbamoylamino]-C-methylcarbonimidoyl]pyridine-3-carboxylic acid | 109293-97-2

• 物质功能分类: 化学试剂 - 有机试剂 - 腙
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(Z)-N-[(3,5-difluorophenyl)carbamoylamino]-C-methylcarbonimidoyl]pyridine-3-carboxylic acid
• CAS: 109293-97-2；1957168-02-3
• 化学式: C₁₅H₁₂F₂N₄O₃
• 分子量: 334.28
• InChiKey: IRJQWZWMQCVOLA-ZBKNUEDVSA-N

物化性质

• 熔点：
  155° (Bowe); also reported as 186° (Anderson).
• 密度：
  0.24 g/cm3(Temp: 25 °C)
• 闪点：
  150 °C
• 颜色/状态：
  Off-white powder, solid
• 气味：
  Odorless
• 溶解度：
  1.88e-04 M
• 蒸汽压力：
  less than 1.3X10-5 Pa /7.50X10-8 mm Hg/ at 20 °C
• 分解：
  When heated to decomposition it emits toxic vapors of /nitrogen oxides and hydrogen fluoride/.
• 解离常数：
  pKa = 3.18

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

ADMET

代谢

尿液、胆汁和粪便的代谢物分析是通过薄层色谱（TLC）、高效液相色谱（HPLC）、质谱和核磁共振光谱进行的。未改变的试验物质是所有排泄物中的主要标记化合物。主要的代谢反应包括环化、水解和羟基化，产生了7种主要代谢物（M1、M2、M5、M6、M9、M10和M19）。M19、M10和M9也在山羊和母鸡的排泄物以及玉米青贮饲料中被识别出来。

Metabolite analysis of the urine, bile and feces was conducted by TLC, HPLC, mass spectrometry and NMR spectroscopy. Unaltered test article was the major labeled compound in all excreta. Major metabolic reactions included cyclization, hydrolysis and hydroxylation, yielding 7 major metabolites (M1, M2, M5, M6, M9, M10 and M19). M19, M10 and M9 were also identified in excreta from goats and hens, and in corn silage.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性数据

大鼠LC50 >2,930毫克/立方米

LC50 (rat) >2,930 mg/m3

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

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，让患者身体前倾或将其置于左侧（如果可能，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：家兔急性暴露/初级眼刺激；轻度到中度刺激（7天内解决）。

/LABORATORY ANIMALS: Acute Exposure/ Primary Eye Irritation in Rabbits; mild to moderate irritation (resolved within 7 days).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给予大鼠后，氟氯苯并吡唑部分吸收并迅速消除；剂量的20-40%通过尿液排出，49-79%通过粪便排出。相比之下，静脉给药的大鼠在尿液中排出了剂量的61-89%。尿液和粪便中的消除半衰期为6小时。

Following oral administration /in rats/, Diflufenzopyr was partially absorbed and rapidly eliminated; 20-40% of the dose was eliminated in urine and 49-79% in feces. By contrast, intravenously dosed rats excreted 61-89% of the dose in urine. Elimination /half-time/ in urine and feces was 6 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

diflufenzopyr 在蛋鸡和哺乳山羊体内的代谢研究。数据显示， diflufenzopyr 能迅速从动物体内排出。在饲料中添加量为10 ppm时，食用组织、牛奶和鸡蛋中的残留水平低于0.12 ppm。...

A metabolism study of diflufenzopyr was conducted in laying hens and lactating goats. The data showed diflufenzopyr was rapidly eliminated from the animals. With a feeding level of 10 ppm in the diet, residue levels in edible tissues, milk, and eggs were less than 0.12 ppm. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

维斯特大鼠根据四种方案接受了(14)C标记的Diflufenzopyr（SAN 835 H苯基标记：放射性纯度> 98%; 吡啶基标记：放射性纯度> 98%; 未标记测试样品纯度= 99.4%）给药：1）单次静脉给药1 mg/kg，2）单次口服给药10 mg/kg，3）单次口服给药1000 mg/kg，4）连续14天口服给予未标记测试样品10 mg/kg，随后单次口服给予标记化合物10 mg/kg。对于方案1、2和3，根据以下3个时间表，对5只雄性和5只雌性进行监测：a) 给药后72小时处死，b) 给药后24小时处死，c) 胆管插管的动物在给药后48小时处死。对于重复给药方案，5只雄性和5只雌性在用标记测试文章给药后24小时和72小时处死。静脉给药导致两种标记形式的快速消除，大约7小时内在尿液中消除58-68%，72小时内消除70-90%。在大约7-20%通过粪便排出的物质中，几乎全部是由于胆汁排泄。口服给药10和1000 mg/kg导致两种标记主要通过粪便消除（72小时内大约55-80%）。尿液中的排出量大约占20-39%，胆汁中排出大约3-10%。72小时后，无论是静脉给药还是口服给药，组织保留都很低，对于苯基标记化合物（血液中最高）保留为0.37%或更低，对于吡啶基化合物（肾脏和肝脏中最高）保留为0.04%或更低。两种标记化合物的吸收百分比，通过将口服给药后尿液中排出的标记化合物量除以静脉给药后排出的量来计算，在30-50%之间，10和1000 mg/kg剂量水平之间没有差异。... 在测试文章的吸收、消除、组织分布或代谢方面，雄性与雌性之间没有显著差异。同样，高剂量和低剂量水平给出了相似的结果，这表明吸收或消除没有饱和。吡啶基标记化合物的组织保留较少，而苯基标记化合物在血液中的保留较多。最后，单次给药与多次给药的对比表明，测试文章不会生物累积或诱导代谢酶。

Wistar rats were administered (14)C-labeled Diflufenzopyr (SAN 835 H phenyl-labeled: radiochemical purity > 98%; pyridinyllabeled: radiochemical purity > 98%; unlabeled test article purity = 99.4%) according to each of four protocols: 1) a single i.v. dose at 1 mg/kg, 2) a single oral dose at 10 mg/kg, 3) a single oral dose at 1000 mg/kg, 4) fourteen daily oral doses of unlabeled test article at10 mg/kg followed by a single oral dose of labeled compound at 10 mg/kg. For protocols 1, 2 and 3, five males and five females were monitored according to each of 3 schedules: a) until sacrifice at 72 hrs post-dosing, b) until sacrifice at 24 hrs post-dosing, c) bile-duct cannulated animals followed until sacrifice at 48 hrs post-dosing. For the repeated dosing protocol, five males and five females were sacrificed at 24 hrs and 72 hrs after dosing with the labeled test article. Intravenous administration led to rapid elimination in the urine of between approximately 58 and 68% of both labeled forms by 7 hrs, and between 70 and 90% by 72 hrs. Of the approximate 7-20% excreted in the feces, almost all was a result of bilary excretion. Oral dosing at both 10 and 1000 mg/kg resulted in elimination of both labels mainly through the feces (approximately 55-80% by 72 hrs). Excretion in the urine accounted for approximately 20-39%, with approximately 3-10% excreted in the bile. Tissue retention at 72 hrs was low after either intravenous or oral dosing, being 0.37% or less for the phenyl-labeled compound (highest in blood) and 0.04% or less for the pyridinyl compound (highest in kidney and liver). The percent absorption for both labeled compounds, calculated by dividing the amount of labeled compound excreted in the urine after oral dosing by the amount excreted in the urine after i.v. dosing, was between 30 and 50%, with no difference between the 10 and 1000 mg/kg dose levels. ... There were no significant differences in test article absorption, elimination, tissue distribution or metabolism by males versus females. Likewise, high and low dose levels gave similar results, suggesting no saturation for absorption or elimination. There was less tissue retention of the pyridinyl-labeled compound and greater retention of the phenyl-labeled compound in the blood. Lastly, single versus multiple dosing showed that the test article did not bioaccumulate or induce metabolizing enzymes.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• RTECS号：
  US5648931
• 海关编码：
  2933399090

制备方法与用途

氟吡草腙概述

氟吡草腙是一种缩氨基脲类、硫代缩氨基脲类和异硫代缩氨基脲类化合物，用于控制杂草。如果吸入氟吡草腙，请将患者移到新鲜空气处；若皮肤接触，应脱去污染的衣物，用肥皂水和清水彻底冲洗皮肤，如有不适感，请就医。

化学性质

氟吡草腙纯品为灰白色无味固体，熔点为135.5℃。其蒸气压在20/25℃时为(1 \times 10^{-7}) mPa。分配系数Kow lgP为0.037（pH 7）。Henry常数小于7×10^-5 Pa ·m^3/mol (20℃)。相对密度在25℃下为0.24。水中溶解度（25℃，mg/L）：pH 5时为63，pH 7时为5850，pH 9时为100,546。水解半衰期DT₅₀：pH 5时为13天，pH 7时为24天，pH 9时为26天。水溶液光解半衰期DT₅₀：pH 5时为7天，pH 7时为17天，pH 9时为13天。pKa值为3.18。

制备

氟吡草腙的制备如下：将含有4-苯基氨基脲（0.37克，2.4毫摩尔）的5毫升甲醇溶液加入到2-乙酰基烟酸（0.40克，2.4毫摩尔）在7毫升甲醇中的水溶液中。混合物在室温下搅拌过夜后，用过滤收集固体沉淀，然后用乙醇洗涤并干燥，得到2-乙酰基烟酸4-苯基缩氨基脲，熔点为174℃（分解）。

作用机理与特点

氟吡草腙通过在蛋白质膜处与载体蛋白结合，抑制生长素的极性运输。与麦草畏混用时，可引导麦草畏向生长点运输，从而增加对阔叶杂草的效果。玉米的耐药性是由于其代谢迅速。这是一种内吸苗后除草剂，敏感的阔叶植物在几个小时内会表现出偏上性生长，而敏感的杂草则表现为生长迟缓。

应用

氟吡草腙可用于玉米、草场/牧场和非作物地区，用于苗后控制一年生阔叶杂草和多年生杂草。最初商品化时与麦草畏混配，两种原料均为钠盐。

毒性

雄性和雌性大鼠经口LD₅₀大于5.0 g/kg；经皮LD₅₀亦大于5.0 g/kg。对兔眼睛具有中度刺激，但对兔皮肤无刺激作用，且对豚鼠皮肤无致敏性。大鼠急性吸入LC₅₀为2.93 mg/L。狗的NOAEL（1年）为750 mg/L[雄性26 mg/(kg·d)，雌性28 mg/(kg·d)]。EPA建议ADI (aRfD) 为1.0 mg/kg，cRfD 为0.26 mg/kg [1999年]。氟吡草腙无致畸、致癌作用。

文献信息

• US5098466A
  申请人：——

  公开号：US5098466A

  公开（公告）日：1992-03-24