4 Sprague Dawley CRL:CD (SD) BR rats per sex per group received a single oral (gavage) dose of [14C]-phenyl labeled AE F130360 at 10 and 1000 mg/kg. Another 2 animals per sex were dosed by gavage with [14C]-pyrimidyl labeled AE F130360 at 10 mg/kg. Urine and feces were collected separately at 6 (urine only), 12 (urine only), 24, 48, and 72 hours post-dosing for quantification of radioactivity. Expired air was not sampled since preliminary work indicated this was a minor route of excretion. The majority of the administered dose irrespective of dose level, sex, or radiolabel was excreted as unchanged parent compound in the feces. Over the 72 hour period following dosing with [14C]-phenyl labeled AE F130360 at 10 mg/kg, 73.999% (males) and 72.337% (females) of the administered dose was found in feces as AE F130360. Cleavage product AE F153745 (4-formylamino-N,N-dimethyl-2-sulfamoyl-benzamide) accounted for 8.417% and 8.671% in males and females respectively, and, a polar unknown, made up 0.176% and 0.095% respectively. The majority was excreted during the first 24 hours, except for the polar unknown, most of which was found at 48 hours. Cleavage product AE F153745 was the most prevalent metabolite in urine, accounting for 2.250% (males) and 2.300% (females) of administered phenyl radiolabel (10 mg/kg) over 72 hours. Parent compound, AE F130360, was 1.723% (males) and 2.128% (females). Free amine, AE F130619 (4-amino-2-3[-(4, 6-dimethoxypyrimidin-2-yl)-ureidosulfonyl)-N,N dimethylbenzamide), was found as 0.831% (males) and 0.777% (females) of administered dose. The polar unknown was present at 0.023% for both sexes. The majority was excreted 6 hours post-dosing. The polar unknown was found at 48 hours. At 1000 mg/kg of [14C]-phenyl labeled AE F130360, 80.360% (males) and 77.732% (females) was excreted in feces as AE F130360 over 72 hours. The polar unknown accounted for 5.856% (males) and 5.637% (females); AE F153745 for 3.381% (males) and 1.264% (females); and AE F130619 for 0.489% (males) and 2.773% (females). The majority of each compound was excreted 24 hours post dosing. ...
/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/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于昏迷、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/
/SIGNS AND SYMPTOMS/ Harmful if swallowed. Causes moderate eye irritation. Avoid contact with eyes, skin or clothing. Prolonged or frequently repeated skin contact may cause allergic reaction in some individuals.
/ALTERNATIVE and IN VITRO TESTS/ Duplicate cultures of pooled human (males) lymphocytes in whole blood were exposed to Hoe 130360 technical (98.4% foramsulfuron), in the presence and absence of rat liver S9, at concentrations of 0 (ethanol), 18.8, 37.5, 75.0, 150, 300, 600, 1200, or 2400 ug/mL. There were duplicate cultures per concentration with three trials at 2400 ug/mL. Test article was added to 48-hour cultures stimulated with PHA. Exposure -S9 was for 21 hours and 45 hours. With S9, treatment was for 3 hours followed by 18-hour or 42-hour incubation after removal of the foramsulfuron. At 150 ug/mL and higher, a precipitate formed at dosing, but was generally not apparent at the end of the treatment period. A slight increase in the number of aberrant cells was noted at 2400 ug/mL in the absence of activation.
12 Sprague Dawley CRL:(IGS) CD BR rats per sex received single daily oral (gavage) doses of [14C]-phenyl AE F130360 at 10 mg/kg for up to 14 days. 3 /rats/ per sex were sacrificed 24 hours after 1, 9, and 14 days of treatment. The majority of tissues were found to have residue levels below 0.01 ug AE F130360/g 24 hours after a single oral dose. Liver contained the highest concentrations of residues (0.079 ug/g and 0.114 ug/g for males and females respectively). 24 hours after the last of 14 daily doses, residues in tissues were mostly below 0.03 ug/g, except for testes (0.073 ug/g), skin (0.042 ug/g in males and 0.166 ug/g in females), and liver (0.222 ug/g and 0.280 ug/g for males and females respectively). Elimination of [14C]-phenyl AE F130360 and its metabolites 48 hours after repeated daily dosing for 14 days was mainly in the feces where 60.99 +/- 22.19% (males) and 88.4 +/- 5.21% (females) of recovered radioactivity was found. Urine was a minor route of elimination. 4.00% (males) and 5.27% (females) was present as parent compound, AE F130360, 48 hours after daily dosing for 14 days. Cleavage product AE F153745 (4-formylamino-N,N-dimethyl-2-sulfamoyl-benzamide) accounted for 4.08% (males) and 2.41% (females), and, the free amine, AE F130619 (4-amino-2-3[-(4, 6-dimethoxypyrimidin-2-yl)-ureidosulfonyl)-N,N dimethylbenzamide), made up 3.50% (males) and 1.65% (females) of recovered label.
6 bile duct cannulated male Sprague Dawley (Crl:CD BR) rats received a single oral (gavage) dose of AE F130360 [phenyl-U-14C] at 10 mg/kg. Four animals were selected for evaluation based on the production of bile. Urine and feces along with cage debris and cage washings were collected pre-dose, 24, and 48 hours post-dosing. Bile was collected at pre-dose, 2, 4, 6, 12, 24, and 48 hours post-treatment. Animals were then sacrificed and the radioactivity as percentage of administered dose was quantified for the carcass. Approximately 17% of the administered dose was absorbed. The largest part of that was found in the urine (12.67% +/- 3.7). Bile accounted for about a quarter (4.198% +/- 1.872). The majority of the administered dose was not absorbed, 75.63% +/- 10.64 was excreted in the feces.
[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] 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.
