... To investigate the relation between metabolism and toxicity of 1,2-dichlorobenzene (1,2-DCB), the biotransformation, tissue distribution, blood kinetics, and excretion at three different oral dose levels (5, 50 and 250 mg/kg) of the radiolabelled compound were investigated in the male Wistar rat. A toxic dose level (250 mg/kg...) was included. ... The concentration of parent chemical was essentially constant during 3 and 6 hr for the mid- and high-dose level respectively, and then declined. 1,2-DCB could only be detected in blood in the first 2 hr after administration of the 5-mg/kg dose. The major route of biotransformation was via the glutathione pathway and 60% of the urinary metabolites were mercapturic acids. In addition, the major metabolites in bile were conjugates of glutathione. Other major metabolites in urine were the sulfate conjugates of 2,3- and 3,4-dichlorophenol (DCP). No significant differences in metabolic profiles were observed between the different doses. Induction with phenobarbital resulted in the increased excretion of sulfate conjugates (30% in the induced rat, 20% in the control rat), mainly the conjugate of 3,4-DCP...
1,2-Dichlorobenzene gave 3,4-dichlorophenol with smaller amounts of 2,3-dichlorophenol, 3,4- and 4,5-dichlorocatechol and 3,4-dichlorophenylmercapturic acid also observed; 1,3-dichlorobenzene gave 2,4-dichlorophenol as the major product with 3,5-dichlorophenol, 3,4-dichlorocatechol, and 2,4-dichlorophenylmercapturic acid also identified; 1,4-dichlorobenzene gave 2,5-dichlorophenol as the major metabolite with 2,5-dichlorquinol identified as a minor product.
来源:Hazardous Substances Data Bank (HSDB)
代谢
3,4-二氯苯酚是1,2-二氯苯的人类已知代谢物。
3,4-dichlorophenol is a known human metabolite of 1,2-dichlorobenzene.
来源:NORMAN Suspect List Exchange
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Neurotoxin - Other CNS neurotoxin
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.
Nephrotoxin - The chemical is potentially toxic to the kidneys in the occupational setting.
Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect
Dermatotoxin - Skin burns.
IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Phenols and related compounds/
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 necessary. 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 ... . Administer activated charcoal ... . Do not use emetics. Cover skin burns with dry, sterile dressings after decontamination ... . Maintain body temperature. /Phenols and related compounds/
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 ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. DIRECT PHYSICIAN ORDER ONLY ... Treat seizures with diazepam or lorazepam. ... Use proparacaine hydrochloride to assist eye irrigation ... . /Phenols and related compounds/
Because of their high lipid solubility and low ionization at physiological pH, dichlorophenols would be expected to be readily absorbed following ingestion. /Dichlorophenols/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
二氯酚同分异构体通过皮肤和肠道被吸收。/二氯酚同分异构体/
Dichlorophenol isomers are absorbed through the skin and from the gut. /Dichlorophenol isomers/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
易于从胃肠道和注射部位吸收。/氯酚/
... Readily absorbed from the gastroenteric tract and from parenteral sites of injection. /Chlorophenols/
Synthesis and in vitro antimycobacterial and isocitrate lyase inhibition properties of novel 2-methoxy-2′-hydroxybenzanilides, their thioxo analogues and benzoxazoles
Mycobacterium avium 330/88, Mycobacterium kansasii 235/80, clinically isolated M. kansasii 6509/96 and the ability to act as in vitro isocitratelyase inhibitors. The best ICL inhibitors were two compounds from the thiobenzanilide group (8f, 8m), which exhibited an inhibition potential that was equal to the standard compound, 3-nitropropionic acid. In addition, the best antimycobacterial properties were
The present invention provides novel compounds that affect excitatory amino acid receptors and are useful in the treatment of neurological disorders. This invention also provides synthetic methods for the preparation of the novel compounds.
Compounds and uses thereof for decreasing activity of hormone-sensitive lipase
申请人：——
公开号：US20030166644A1
公开（公告）日：2003-09-04
Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.
[EN] GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE GLYCOLATE OXYDASE POUR LE TRAITEMENT D'UNE MALADIE
申请人：BIOMARIN PHARM INC
公开号：WO2020257487A1
公开（公告）日：2020-12-24
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
