Several metabolites of pyriminil have been identified including aminopyriminil, acetamidopyriminil, p-aminophenyl urea, p-acetamidophenyl urea, p-nitroaniline, p-phenylenediamine, p-acetamidoaniline, nicotinic acid, nicotinuric acid & nicotenamide. Most of these metabolites were found in the urine of poisoned rats, dogs & people, but in different concentrations.
Repeated, sublethal doses of pyriminil incr the urinary & fecal excretion of latter dose of the cmpd tagged with (14)C; however, these same animals showed increased hexobarbital sleeping times & other evidence of inhibition of certain liver microsomal enzymes, especially p-nitro-anisole O-demethylase.
Analysis of liver from a human poisoning case demonstrated the presence of PNU & p-nitroaniline. It was suggested that p-nitroaniline was formed by amide hydrolysis of PNU.
Hepatic metabolism of the rodenticide RH-787 (N-3-pyridyl- methyl-N'- p-nitrophenyl urea) plays a key role in species sensitivity differences. 3-MC pretreatment of rats enhanced their hepatic extraction of 14C-787, increased biliary secretion of its metabolites and protected them against 787 toxicity. Dogs natively showed more efficient hepatic extraction of 787, leading to its rapid metabolic degradation. Rats tolerated chronic sublethal 787 levels, but most tissues showed 14C accumulation after multiple 14C-787 doses. Since this was more pronounced for pyridyl- than nitrophenyl-14C, metabolic cleavage products were suspected. Pretreatment of rats with multiple 787 doses enhanced urinary and fecal 14C excretion after pulse doses of 14C-787, but prolonged hexobarbital sleeping times and strongly inhibited hepatic p-nitroanisole O-demethylation in vitro; the latter was also inhibited by direct in vitro 787 addition. Antidotal levels of nicotinamide (NA) did not prevent MFO inhibition by 787, but altered 14C-787 disposition. Higher NA levels also inhibited the MFO. High affinity for microsomal enzymes may explain NAD-antagonism by 787 via glycohydrolase and make it useful as a model compound. Concentrates of urinary and biliary 787 metabolites and synthetic metabolites (amino-787, p-nitroaniline, p-nitrophenyl urea) were less toxic than 787.
Species selectivity of RH-787 (N-3-pyridylmethyl- N'-p-nitrophenyl urea) seems to depend on biotransformation. These studies compared fates of Py- and NP-14C-787 in rats and dogs. Human Vacor (pyriminil) metabolites were examined in poisoning cases. Although single oral 30 mg/kg doses of 787 were lethal to rats but not dogs, they produced higher blood levels in dogs. However, most 14C in rat blood was due to 787, while dog blood contained primarily p-nitrophenyl urea. Rat urine contained large amounts of 787 while dog urine had < 1%. Dog urine contained 40-60% unidentified polar material, but rat urine only 5-20%; this material from rats, but not dogs, was partially hydrolyzed by beta-glucuronidase to 787. Other identified metabolites include amino-787, acetamido-787, p-aminophenyl urea, p-acetamidophenyl urea, p-nitroaniline, p-phenylenediamine, p-acetamidoaniline, nicotinic acid, nicotinuric acid and nicotinamide. Most were found in all three species, but concentrations varied. The presence of parent compound in rat and human urine suggests that they may be more sensitive to Vacor because of inefficient metabolism. Tolerance in dogs is probably due to rapid detoxication.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Whatever microsomal enzymes are responsible for metabolism of pyriminil are induced by pretreatment with 3-methylcholanthrene, which increases biliary excretion of the metabolites and decreases pyriminil toxicity 50-fold.
... The antidotal efficacy of nicotinamide (p.o. or i.p.) was greatest when administered within 1 hr of Vacor, or when pre-fed in diet. Nicotinic acid was less effective. Rats fed high levels of L-tryptophan or acutely pretreated were protected against Vacor, while D-tryp. and other amino acids were less effective. Agents such as atropine, PAM or nikethamide delayed but did not prevent death. Vacor or 2,4-DNP caused similar symptoms, suggesting interference with mitochondrial respiration. While mild Vacor-induced hyperglycemia was seen in rats and reversed by insulin, its role in ultimate toxicity is unclear. Vacor biotransformation appears to be more significant in detoxication, but prior bioactivation was not necessarily excluded. Cyt. P-448 induction by 3-MC pretreatment decreased Vacor toxicity 50-fold, while other classes of MFO inducers (PB, DMSO, PCN) did not significantly alter its potency. Reduction of P-450 complex activity by starvation or CS2 pretreatment potentiated the toxicity, but SKF-525A delayed death. Pretreatment with diethyl maleate, cobaltous chloride, or neomycin did not significantly alter Vacor toxicity.
Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/
Rats tolerated, metabolized, & eliminated single or multiple sublethal dosages (5 mg/kg) but were less efficient than dogs in detoxifying dosages in excess of 20 mg/kg. It was concluded that the tolerance of dogs for the cmpd depended on their efficient hepatic extraction, metabolism, & excretion of it. The urine of poisoned rats & people contained the parent cmpd but the urine of dogs that had received it contained < 1%.
These studies compared the disposition of pyridyl- and nitrophenyl-1 [14C]RH-787 in tolerant and susceptible species. The compound was rapidly absorbed by rats, mice, and dogs after oral administration. Blood levels peaked in 1 to 6 hr, depending on species and label, and were higher after NP- than Py[14C] administration in each species. Doses of 30 mg/kg produced higher 14C levels in dogs than in rats-yet such dose levels are lethal to rats, but not dogs. G.I. transit of 14C was more rapid in dogs than in rats. Urinary and fecal excretion were of similar importance in all three species; NP label was more rapidly eliminated. Tissue distribution of two 14C labels varied, especially in dogs-suggesting more extensive metabolism. Liver contained more of the dose than any other single organ. Most hepatic 14C was located in the cytosol of each species, but rats and dogs differed in nuclear and microsomal fractions. Label differences in subcellular distribution were small when expressed as percentages of total liver 14C. Most 14C was reversibly bound to various organelle pellets. Rats tolerated, metabolized, and eliminated single or multiple sublethal RH-787 doses (5 mg/kg), but their metabolic systems were less efficient thant those of dogs for detoxifying larger doses (> 20 mg/kg). Pretreatment of rats with 3-MC enhanced their hepatic extraction of RH-787, increased biliary secretion of its metabolites, and protected rats against RH-787 toxicity. Thus, RH-787 tolerance in dogs seems to be related to effiicient hepatic extraction, followed by rapid metabolic degradation and excretion.
Binding of Polyatomic Anions with Protonated Ureido-pyridyl Ligands
摘要：
Two ureido-pyridyl ligands, 1-(4-nitro-phenyl)-3-pyridine-3-ylmethyl-urea (L-1) and 1-pentafluorophenyl-3-pyridine-4-yl-urea (L-2) were synthesized in good yields, and solid-state anion binding studies of (HL1)(+) and (HL2)(+) with polyatomic anions such as NO3-, AcO-, ClO4-; SO42-, and SiF62- were carried out in detail. Protonation of the pyridyl nitrogen center of L-1 with HNO3, HClO4, and HF in different solvent media yielded crystals of complexes 1 (HL1 center dot NO3), 2 (HL1 center dot ClO4), and 3 (HL1 center dot 0.5SiF(6)) suitable for single crystal X-ray diffraction studies; respectively. Similarly, protonation of L-2 with HNO3, CH3COOH, and H2SO4 yielded single crystals of complexes 4 [2(HL2 center dot NO3)center dot DMF], 5 (HL2 center dot AcO), and 6 [(HL2)(2)center dot SO4], respectively. X-ray crystallographic analysis of all these six complexes has been carried out and the details of anion binding with the urea functionality of ureido-pyridyl ligands were investigated. In all the complexes, the pyridyl moiety of the ligands is found to be protonated and the binding of anions are observed at the urea functionality of the ligands through the R-2(2)(8) hydrogen bonding motif irrespective of sizes and shapes of anions or the electron withdrawing ability of aryl substitutions (p-nitro phenyl vs pentafluoro phenyl) or the position of the pyridyl nitrogen center (protonation site) of the designed ligands.
[EN] POLYAMIDES FUNCTIONALIZED WITH CHAINS CONTAINING THIOL FUNCTIONS [FR] POLYAMIDES FONCTIONNALISÉS AVEC DES CHAÎNES CONTENANT DES FONCTIONS THIOL
摘要：
A polyamide comprising monomer units containing at least one elementary unit according to formula (I), wherein R1is a linear alkyl containing 1 to 6 carbon atoms; and wherein R2is an aliphatic chain containing 1 to 30 carbon atoms selected among one of the followings: an alkyl chain, an alkenyl chain, an alkynyl chain, eventually containing at least one of the following atoms or groups: O; N; S; -CO-; -CO-O-; -CO- N-; -CO-S-; carbonate; carbamate; urea; phosphate; phosphonate; sulfoxide; sulfone; cycloalkyl; aryl and heteroaryl; the cycloalkyl, aryl and heteroaryl being eventually substituted by one of the following: alkyl; hydroxy; hydroxyalkyl; alkyloxy; halogen; cyano; -SH; nitro; thioalkyl and alkylthio.
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。
[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。
Novel insecticides
申请人：Syngenta Participations AG
公开号：EP2540718A1
公开（公告）日：2013-01-02
Compounds of formula I
wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts and all stereoisomers and tautomeric forms of the compounds of formula I can be used as insecticides and can be prepared in a manner known per se.
Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
申请人：Dow AgroSciences LLC
公开号：US20180279612A1
公开（公告）日：2018-10-04
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).
[EN] MOLECULES HAVING PESTICIDAL UTILITY, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES, RELATED THERETO<br/>[FR] MOLÉCULES PRÉSENTANT UNE UTILITÉ EN TANT QUE PESTICIDE, ET LEURS INTERMÉDIAIRES, COMPOSITIONS ET PROCÉDÉS
申请人：DOW AGROSCIENCES LLC
公开号：WO2017040194A1
公开（公告）日：2017-03-09
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions aga inst such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula ("Formula One").
