Four male Fischer 344 rats/group were dosed once orally by gavage with 1000 (Group A) or 50 mg/kg (Group B) of (14)C Aminopyralid (XDE-750-pyr-2,6-(14)C) (radiochemical purity: 98.6%, specific activity: 27.4 mCi/mmol) or for 14 days with 50 mg/kg/day of Aminopyralid (purity: 99.5%), followed by a single dose of 50 mg/kg (Group C) of the radiolabeled compound. Urine and fecal samples were collected for up to 168 hours post-dose. ... In the urine, 96% of the administered dose was unmetabolized parent compound. In the feces, 100% of the administered dose was unmetabolized.
/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：对于失去意识、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5%葡萄糖水（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%盐水（NS）或乳酸林格液。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/
/LABORATORY ANIMALS: Acute Exposure/ Groups of five overnight-fasted male and female Fischer 344 rats received aminopyralid (purity: 94.5%) at a dose of 5000 mg/kg bw by gavage as two doses at 2500 mg/kg administered with an interval of 1 hr, as a 50% mixture in 0.5% aqueous methylcellulose. The rats were observed for mortality, clinical signs and body-weight development during the 14 days after dosing and were then necropsied. One male rat died on test day 3, its appearance before death being consistent with a moribund condition. Clinical observations in the surviving rats revealed a high incidence of various combinations of perineal, perioral and perinasal soiling, watery faeces and a lower incidence of periocular soiling, decreases in muscle tone, resistance to removal, extensor-thrust, and reactivity to handling were observed. All surviving animals recovered completely by the time of study termination. Four rats had transient body-weight loss during the first week of the study, but all rats gained weight over the duration of the study. On necropsy, the male that died had treatment-related gross findings consisting of haemolysis, gas in the gastrointestinal tract and perineal soiling. Surviving animals had no treatment-related gross pathological changes
/LABORATORY ANIMALS: Acute Exposure/ Groups of five overnight fasted male and female Fischer 344 rats received a single dose of undiluted GF-871 (41.9% aminopyralid TIPA) at a dose of 5000 mg/kg bw (equivalent to a dose of aminopyralid of 1085 mg/kg bw) by gavage. The rats were observed for mortality, clinical signs and body-weight development during the next 14 days and were then necropsied. The study complied with GLP. All animals survived the 14-day observation period and gained weight. Clinical observations consisted of bilateral cloudy eyes in all animals on day 1, lacrimation, watery or soft feces and soiling of the periocular and/or perineal regions. All clinical signs resolved by test day 4. No treatment-related pathological changes were observed. /Aminopyralid TIPA/
Aminopyralid (XDE-750) is rapidly absorbed, distributed and excreted following oral administration. Total 24-hour recoveries of the radioactivity were high for all groups ( about 41-59% and 33-43% of the administered dose in urine and feces, respectively). The absorption and excretion patterns of the (14)C moiety were similar among all groups. ... Tissue distribution and bioaccumulation of XDE-750 were minimal, with <0.73% of the administered dose being recovered in tissues 7 days after oral administration for all dosing groups. Highest levels of radioactivity were found in the skin and carcass. XDE-750 was excreted unchanged indicating an absence of metabolism. Of the total radioactivity in urine, parent accounted for about 96%, and of the total radioactivity in feces, parent accounted for 100%.
Four male Fischer 344 rats/group were dosed orally by gavage with (A) 50 mg/kg of (14)C-Aminopyralid (XDE-750-pyridine-2,6-(14)C) (radiochemical purity: 98.25%, specific activity: 28.6 mCi/mmole) or (B) 96 mg/kg of (14)C Aminopyralid-TIPA (triisopropanolamine) which was prepared from (14)C XDE-750-pyridine-2,6-(14)C with the appropriate amount of triisopropanolamine. Urine, fecal and plasma samples were collected for up to 120 hours post-dose. In the excretion profile, 42 to 46% (urine plus cage wash) and 51 to 54% of the administered dose was recovered in the urine and feces, respectively, for the two groups. The percentage of the administered dose recovered in the first 24 hours post-dose was 93 to 94%. The percentage of the administered dose recovered in the plasma was limited to 0.04 to 0.05% over the time course of sample collection. The peak plasma levels for both dosing regimens was within the first 15 minutes post-dose. ... /Triisopropanolamine salt/
The absorption, distribution, metabolism and excretion of aminopyralid were studied in three groups of three female New Zealand White (NZW) rabbits given single and multiple oral daily doses by gavage. Three non-pregnant animals received a single dose of radiolabelled test material at 371 mg/kg bw, three pregnant animals received a single dose of radiolabelled aminopyralid at 362 mg/kg bw on day 7 of gestation and another three pregnant animals received repeated daily doses of nonlabelled aminopyralid at 279 mg/kg bw from day 7 of gestation until day 21 of gestation, followed by a single dose of radiolabelled aminopyralid at 279 mg/kg bw on day 22 of gestation. The variation between doses administered was the consequence of inadvertently using different dose preparations, but this was judged not to affect the interpretation of the results. ...Additionally, plasma from rabbits that were not pregnant, from pregnant animals on day 7 of gestation and on day 22 of gestation and for comparison purposes from nonpregnant female Fischer 344 rats was used for studies of plasma protein binding with radiolabelled aminopyralid. ... The test material was 94.5% chemically and 98.25% radiochemically pure active ingredient and had a specific activity of 1.058 GBq/mmol. ...There was increased early renal excretion, shorter Tmax and higher plasma area under the curve of concentration-time (AUC) in pregnant rabbits given repeated doses, indicating more rapid and extensive absorption in these animals when compared with non-pregnant rabbit or pregnant rabbits given a single dose on day 7 of gestation. Plasma protein binding of aminopyralid was moderate, about 40-70%, and was greater in rats than in rabbits. In rabbits, it was slightly lower in pregnant animals on day 22 of gestation after pretreatment. In summary, the pharmacokinetic and plasma-protein-binding studies indicated a somewhat higher bioavailability in late-stage pregnant rabbits than in non-pregnant or early-stage pregnant rabbits, although the difference in terms of unbound compound was not more than twofold.
To compare the patterns of absorption, distribution, metabolism and excretion of aminopyralid and aminopyralid TIPA, two groups of four male Fischer 344 rats received single equimolar doses of either (14)C-aminopyralid at 50 mg/kg bw or (14)C-aminopyralid TIPA at 96 mg/kg bw by oral gavage. (14)C-aminopyralid TIPA was prepared using (14)C-aminopyralid by adding appropriate amounts of TIPA. The test material was 94.5% chemically and 98.25% radiochemically pure active ingredient. Both test materials had a specific activity of 1.058 GBq/mmol and were administered in 0.5% methylcellulose in distilled water. Dosing preparations containing aminopyralid (acid form) appeared to be much more like a suspension than did the TIPA salt, which was readily soluble. Aminopyralid was re-suspended before gavage by shaking by hand. Rats were fitted with indwelling jugular vein cannulae and blood samples (14) were taken at intervals until 120 hr after dosing. ... Throughout the study, the animals looked healthy and showed no changes in appearance or behavior. Calculated as the sum of renal excretion and remaining radioactivity in tissues and carcass, 46% and 43% of aminopyralid in the acid form and as the TIPA salt were absorbed, respectively. Fecal excretion amounted to about 50% for both compounds. Except for one male with 0.02% of the administered dose in the skin, no radioactivity at above the limit of quantitation of </= 0.01% of administered dose (LOQ) was recovered in the tissues of rats treated with aminopyralid. In rats treated with aminopyralid TIPA, traces of radioactivity at slightly greater than the LOQ were identified in the kidney and the spleen. Plasma peak concentrations were achieved at 0.25 hr after dosing resulting in 26 and 16 ug acid equivalents/g plasma in rats treated with aminopyralid or aminopyralid TIPA, respectively. For both compounds, urinary excretion was nearly completed within the first 24 hr after dosing and the biphasic elimination parameters were comparable.
Four male Fischer 344 rats/group were dosed once orally by gavage with 1000 (Group A) or 50 mg/kg (Group B) of (14)C Aminopyralid (XDE-750-pyr-2,6-(14)C) (radiochemical purity: 98.6%, specific activity: 27.4 mCi/mmol) or for 14 days with 50 mg/kg/day of Aminopyralid (purity: 99.5%), followed by a single dose of 50 mg/kg (Group C) of the radiolabeled compound. Urine and fecal samples were collected for up to 168 hours post-dose. The excretion profile was characterized, the distribution of radiolabeling in the tissues at 168 hours post-dose was determined and the isolation and identification of the radiolabeled metabolites was attempted. In the excretion profile, 51 to 62% (urine plus cage wash) and 33 to 43% of the administered dose was recovered in the urine and feces, respectively, for the three groups. The percentage of the administered dose recovered in the first 24 hours post-dose was greatest for Group B (94%), declining to 89% for Group C and 74% for Group A. ... The skin was the primary tissue site of recovery at 168 hours post-dose. Otherwise, the radiolabeling was well distributed throughout the other tissues and the carcass except for the fat. ...
Electrophilic fluorination: the aminopyridine dilemma
摘要：
An unusually high yielding fluorination of aminopyralid (3) using F-TEDA (SELECTFLUOR (TM)) in warm water, followed by kinetic resolution (via iterative esterification/saponification) of the crude fluorination product with dry HCl in methanol produced pure ring-fluorinated pyridine 2 in an overall yield of 31% for the two steps. (C) 2009 Elsevier Ltd. 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] 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.
