Ethylhexoic acid is a colorless to light yellow liquid with a mild odor. It will burn though it may take some effort to ignite. It is slightly soluble in water. It is corrosive to metals and tissue. It is used to make paint dryers and plasticizers.
颜色/状态：
Clear liquid
气味：
Mild odor
蒸汽密度：
5.0 (AIR= 1)
蒸汽压力：
0.03 mm Hg at 20 °C
亨利常数：
Henry's Law constant = 2.8X10-6 atm-cu m/mol at 25 °C (est)
自燃温度：
700 °F (371 °C)
分解：
When heated to decomposition, it emits acrid and irritating fumes.
Male Wistar rats receiving 2-ethylhexanoic acid in drinking water (600 mg/kg daily) for 9 weeks eliminated 10 different metabolites, including 2-ethyl-1,6-hexanedioic acid, 2-ethyl-6-hydroxyhexanoic acid, five other hydroxylated metabolites and two lactones, the unsaturated 5,6-dehydro-2-ethylhexanoic acid, and parent compound (partly as the glucuronic acid conjugate).
Major urinary metabolites included the glucuronide of 2-ethylhexanoic acid, the glucuronides of 2-ethyl-6-hydroxyhexanoic acid and 2-ethyl-1,6-hexanedioic acid, and unmetabolized 2-ethylhexanoic acid. The proportions of each metabolite changed with the dose and route of administration.
... Liver microsomes were extracted from male Han/Wistar rats, male DBA/2N/Kuo mice, and humans undergoing liver surgery. 2-Ethylhexanoic acid metabolism was determined in-vitro by incubating the microsomes in the presence and absence of the cytochrome P450 inhibitors triacetyloleandomycin, metyrapone, quinidine, and SKF-525A. In-vivo, 2-ethylhexanoic acid metabolism was determined by administering 2-ethylhexanoic acid to rats with and without the cytochrome P450 inhibitors, and by assessing metabolite levels in human urine samples taken from 2-ethylhexanoic acid exposed sawmill workers. The main 2-ethylhexanoic acid metabolite produced in all microsomes was 2-ethyl-1,6-hexanedioic acid. Production of this metabolite was prevented by triacetyloleandomycin, metyrapone, quinidine, and SKF-525A. /It was/ concluded that some cytochrome P450s may contribute to 2-ethylhexanoic acid metabolism in the liver, that the same 2-ethylhexanoic acid metabolites are formed in rats and humans, and that 2-ethylhexanoic acid resembles the hepatotoxicant 2-envalproic acid.
The metabolites of 2-ethylhexanoic acid ... were investigated in rat urine. Male Wister rats were give 2-ethylhexanoic acid in drinking water 1600 mg/kg daily for nine weeks, and then urine specimens were collected and analysed. ... In addition to 2-(ethylhexyl)adipate, ten different 2-(ethylhexyl)adipate related metabolites were found in the urine of 2-(ethylhexyl)adipate treated rats. The main metabolite was 2-ethyl-1,6-hexanedioic acid. Urine also contained 2-ethyl-6-hydroxyhexanoic acid and five other hydroxylated metabolites and two lactones, the detailed structures of which have not yet been elucidated. The unsaturated 5,6-dehydro-di-2-(ethylhexyl)adipate was also identified; this is the metabolite corresponding to 2-n-propyl-4-pentenoic acid, the hepatotoxic metabolite of valproic acid. At least part of the 2-(ethylhexyl)adipate is present in urine as a glucuronide conjugate.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其蒸汽、透过皮肤和通过摄入被身体吸收。
The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
吸入症状
咳嗽。
Cough.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
皮肤症状
红色。
Redness.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
眼睛症状
红肿。疼痛。
Redness. Pain.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
The disposition of di-2-(ethylhexyl)adipate in humans following administration of the stable isotope labeled test substance was investigated. Blood and urine samples were collected from six male volunteers following the administration of 46 mg of 2H10 labeled di-2-(ethylhexyl)adipate. Blood was collected at 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours after administration. Urine was collected for up to 96 hours after administration. No adverse effects were observed in any of the volunteers and no significant changes in biochemical or hematological parameters were seen. The plasma contained no parent molecule; however, the metabolite 2-ethylhexanoic-acid was detected, but levels were below the limit of quantitation. 2-ethylhexanoic-acid, as a conjugated product, was also the principal metabolite detected in urine. Urinary elimination of the di-2-(ethylhexyl)adipate metabolites peaked within 8 hours of dosing in all volunteers; beyond 36 hours, no metabolites were detected in urine. The conjugated 2-ethylhexanoic acid in urine accounted for an average of 8.6% of the administered dose. A further 3.5% of the dose was accounted for by 2-ethyl-5-hydroxyhexanoic acid, 2-ethylhexanedioic acid, 2-ethyl-5-keto-hexanoic acid, and 2-ethylhexanol. /It was/ concluded that 2-ethylhexanoic acid is an appropriate marker for biological monitoring in estimating the dietary di-2-(ethylhexyl)adipate intake as it is the major metabolite identified and as its rate of elimination is similar to that of other measured di-2-(ethylhexyl)adipate metabolites.
... 2-(14)C-ethylhexanoic acid in rat blood, brain, liver and kidney was quantitated by liquid scintillation analysis and by wholebody autoradiography in mice. A single intraperitoneal dose of 2-(14)C-ethylhexanoic acid was injected in both species. Animals were sacrificed 30 min, 2 and 6 hr after the administration of 2-(14)C-ethylhexanoic acid in autoradiography experiments. The highest uptake of 2-(14)C-ethylhexanoic acid was observed in the liver, kidney and blood in mice. In contrast, low uptake of 2-(14)C-ethylhexanoic acid was seen in the brain. 2-(14)C-ethylhexanoic acid was well detectable in the olfactory bulb and in the salivary gland. In rats, at 2 hr after administration the highest concentration of 2-(14)C-ethylhexanoic acid occurred in blood (0.3%; of the total dose/g tissue). The radioactivity in the liver (0.2%) and kidney (0.1%) was also relatively high. The concentrations of 2-(14)C-ethylhexanoic acid was low in the brain (0.02%). By 6 hr, the radioactivity had decreased rapidly and was hardly measurable at 24 hr after the administration. The results suggest that 2-ethylhexanoic acid is rapidly cleared from the tissues.
[2-14(C)-Hexyl]2-ethylhexanoic acid in corn oil was administered to female Fischer 344 rats either as a single oral gavage at 100 or 1000 mg/kg, or after 14 days of oral unlabeled 2-ethylhexanoic acid (100 mg/kg only). An aqueous solution of [2-14(C)-hexyl]2-ethylhexanoic acid was applied topically at either 100 or 1000 mg/kg and another group of rats received 2-ethylhexanoic acid by intravenous injection (1 mg/kg). Urine, feces, and blood were collected at various intervals for 96 hr. Approximately 72 to 75 percent of the oral dose was excreted in the urine within 24 hr, and <10 percent was excreted after 24 hr. About 50% of the 14(C) was excreted in the first 8 hr after the 100-mg/kg dose versus 20 percent after the 1000 mg/kg dose. Fecal excretion accounted for 7 to 12 percent of both doses. After intravenous injection, 64 percent of the l4(C) was excreted in the urine and 2 percent in the feces. Repeated dosing with unlabeled 2-ethylhexanoic acid (100 mg/kg) appeared to reduce the urinary elimination of 14(C) slightly to 55 percent in urine, whereas the fecal excretion increased to 15 percent in the first 24 hr. After dermal application, approximately 30 percent of the applied dose was excreted in the urine during the first 24 hr, followed by an additional 8 and 17 percent from 24 to 96 hr for the 100- and 1000-mg/kg doses, respectively. Fecal excretion was 7 percent for both dose levels. Dermal absorption was estimated to be 63 to 70 percent relative to intravenous administration. After dermal application, peak blood levels of 14C occurred about 5.7 hr after application and the absorption half-life was 3.2 hr. Major urinary metabolites included the glucuronide of 2-ethylhexanoic acid, the glucuronides of 2-ethyl-6-hydroxyhexanoic acid and 2-ethyl-1,6-hexanedioic acid, and unmetabolized 2-ethylhexanoic acid. The proportions of each metabolite changed with the dose and route of administration.
Nine sawmill workers were divided into two groups according to their exposure to 2-ethylhexanoic acid, a pesticide which has replaced the older pentachlorophenol. The men with lower exposure excreted 30 + or - 10 nmol 2-ethylhexanoic acid/mmol creatinine (mean SD, n = 4) in urine samples taken after the workshift, whereas men with higher exposure excreted 1.8 + or - 1.6 umol 2-ethylhexanoic acid/mmol creatinine (mean + - SD, n = 5, p < 0.01). The urinary ornithine and arginine concentrations were at the lower exposure 1.4 0.4 and 1.5 + or - 0.8 umol/mmol creatinine, respectively (mean + or - SD, n = 4), and they increased significantly (p < 0.01) to 4.5 2.5 and 3.2 + or - 1.5 umol/mmol mean + or - SD, n = 5), respectively, at the higher exposure. This might have been caused by the inhibitory effect of 2-ethylhexanoic acid on urea synthesis which was partially compensated for by elevated arginine and ornithine concentrations to drive the urea cycle more efficiently.
... The hypothesis that infants undergoing exchange transfusion are exposed to toxic levels of di-(2-ethylhexyl)-phthalate and the presumed metabolite 2-ethylhexanoic acid was tested by measuring serum levels of di-(2-ethylhexyl)-phthalate in 16 newborn infants (gas-liquid-chromatography) and urine concentrations of 2-ethylhexanoic acid in 6 of these infants (gas chromatography-mass spectrometry). Di-(2-ethylhexyl)-phthalate levels were undetectable (< 1 ug/mL) before exchange but ranged from 6.1 to 21.6 ug/mL of serum (average, 12.5 to 6.2 ug/mL) after a single exchange transfusion. Di-(2-ethylhexyl)-phthalate uptake did not result in cholestasis. 2-Ethylhexanoic acid peak levels were 127 to 416 ng per mL of urine, with a median of 174 ng per mL. Concentrations of 2-ethylhexanoic acid were lower than anticipated, which indicates that 2-ethylhexanoic acid is not a major metabolite in the neonatal infant.
Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
[EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
申请人：CAMP4 THERAPEUTICS CORP
公开号：WO2019195789A1
公开（公告）日：2019-10-10
The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).
Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.
The present invention relates to a process for preparing polyol esters by reacting polyols with linear or branched aliphatic monocarboxylic acids having 3 to 20 carbon atoms by partial recycling of the aliphatic monocarboxylic acid removed into the esterification reaction or into subsequent esterification batches.
The present invention relates to a process for preparing polyol esters by reacting polyols with linear or branched aliphatic monocarbocxylic acids having 3 to 20 carbon atoms, the reaction taking place in the presence of a Lewis acid comprising at least one element from groups 4 to 14 of the Periodic Table of the Elements as catalyst, and in the presence of an adsorbent, the reaction product being subjected subsequently to a steam treatment.
