N-butyl-p-hydroxybenzoate appears as odorless white crystals or crystalline powder. Tasteless, but numbs the tongue. Aqueous solutions slightly acidic to litmus. (NTP, 1992)
颜色/状态：
Small, colorless crystals or powder
气味：
Odorless
蒸汽压力：
2.51X10-4 mm Hg at 25 °C (est)
稳定性/保质期：
Stable under recommended storage conditions.
自燃温度：
495 °C
分解：
When heated to decomposition it emits acrid smoke and irritating fumes.
In mice, rats, rabbits, or dogs, butyl paraben is excreted in the urine as unchanged benzoate, p-hydroxybenzoic acid, p-hydroxyhippuric acid (p-hydroxybenzoylglycine), ester glucuronides, ether glucuronides, or ether sulfates.
By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /4-Hydroxybenzoates (Parabens)/
The penetration and metabolism of butylparaben using viable, full-thickness human skin /is described/. ... A total of 21% of the radiolabel penetrated to the receptor fluid after 24 hr. ... the principle metabolite, hydroxybenzoic acid, was detected in the receptor fluid, with barely detectable levels of butylparaben and no ethylparaben, in this study of full-thickness skin. ... This work was repeated to again examine the penetration and metabolism of butylparaben (0.4%) in an oil/water emulsion applied to the same full thickness viable human skin ... A finite dose (10 L/cm ) of the 2 emulsion was applied to the skin surface and remained in contact over a 24 hr period without occlusion. (14)C-butylparaben (labeled in the carbon ring) was measured in the receptor fluid. A mean value of 14.9% (+ or - 3.73%) of the radioactive label penetrated the full thickness human skin after 24 hr. The principle metabolite, hydroxybenzoic acid, was found in the receptor fluid (mean of 15.2% + or - 5.23%) of all 10 replications (skin donated from two individuals), but barely detectable levels of the parent butylparaben (mean of 0.225% 0.063%) were found only in 5 of 10 replications. The authors interpreted these results to confirm the near complete first-pass metabolism of butylparaben to p-hydroxybenzoic acid in human skin.
... A study /was conducted/ of the in vitro dermal penetration and metabolism of methylparaben and butylparaben in rat and human skin. For each paraben, an oil in water emulsion with both radiolabeled ( C in the carbon 14 ring) and non-radiolabeled paraben was prepared to a target concentration (0.8% for methylparaben and 0.4% for butylparaben). Skin samples (10 replicates for rat skin and 13 replicates for human skin) were mounted in flow-through diffusion cells. Test emulsions were applied evenly at 10 L/cm , one time, with no occlusion. Samples of the receptor 2 fluid from a single skin were pooled, along with reference standards, were mixed with acetonitrile, filtered, and analyzed for methylparaben, butylparaben, and hydroxybenzoic acid using liquid chromatography coupled with mass spectroscopy. ... For Butylparaben, 52.3% was metabolized to hydroxybenzoic acid, with only 5.5% as unmetabolized butylparaben. Metabolism was different in human skin ... For butylparaben, 32.8% appeared as hydroxybenzoic acid and 49.7% as unmetabolized butylparaben.
IDENTIFICATION AND USE: HUMAN EXPOSURE AND TOXICITY: Butylparaben was a skin irritant in man. Experimental studies in volunteers failed to uncover any sensitizing potential, but sensitization to butylparaben has been demonstrated in dermatitis patients. ANIMAL STUDIES: A low acute oral toxicity was seen in mice treated with the ester whereas the sodium salt was of moderate toxicity. In mice, there were effects on the spleen and thymus as well as liver damage. Butylparaben in the diet produced cell proliferation in the forestomach of rats, but it was noncarcinogenic in a mouse chronic feeding study. It was not mutagenic in Ames bacterial tests. In one in vitro study, sperm were not viable at concentrations as low as 1 mg/mL for butylparaben. Epididymis and seminal vesicle weight decreases were reported in rats given a 1% oral butylparaben dose; and decreased sperm number and motile activity in F(1) offspring of rats maternally exposed to 100 mg/kg per day were reported. Decreased sperm numbers and activity were reported in F(1) offspring of female rats given Butylparaben by subcutaneous injection at 100 or 200 mg/kg per day, but there were no abnormalities in the reproductive organs. Butylparaben does bind to estrogen receptors in isolated rat uteri, but with an affinity orders of magnitude less than natural estradiol. ECOTOXICITY STUDIES: The aquatic toxicity on fish, daphnia, and algae was weaker for the parabens with a shorter alkyl chain than those with a longer alkyl chain as predicted by their hydrophobicity. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100 ug/L n-butylparaben, i-butylparaben for 14 days. In a rainbow trout Oncorhynchus mykiss increases in average plasma vitellogenin levels were seen at oral exposure to 9 mg butylparaben/kg for 2 days. In other experiment, butylparaben was estrogenic at 10 mg/kg bw in rainbow trout.
来源:Hazardous Substances Data Bank (HSDB)
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).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
副作用
职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。
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.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The individual and combined (binary mixtures) (anti)androgenic effect of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) was evaluated using the MDA-kb2 cell line. Exposing these cells to AR agonists results in the expression of the reporter gene (encoding for luciferase) and luminescence can be measured in order to monitor the activity of the reporter protein. In case of the evaluation of the anti-androgenic effect, the individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a strong AR agonist (1000 pM 5-alpha-dihydrotestosterone; DHT). Cell viability was assessed using a resazurin based assay. For PG, this is the first report in the literature concerning its (anti)androgenic activity. In case of both individual and mixture testing none of the compounds or binary combinations showed androgenic activity. When tested in the presence of DHT, BuPB, BHA and BHT proved to be weak anti-androgens and this was confirmed during the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT and BHA+BHT). Besides performing the in vitro testing of the binary combinations, two mathematical models (dose addition and response addition) were evaluated in terms of accuracy of prediction of the anti-androgenic effect of the selected binary mixtures. The dose addition model guaranteed a good correlation between the experimental and predicted data. However, no estimation was possible in case of mixtures containing PG, due to the lack of effect of the compound in case of the individual testing.
Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) (ranging from 10(-9) to 10(-7) m [1-100 nm; 0.39-39 ng/mL ]) and butylparaben (BP) (ranging from 10(-8) to 10(-5) m [10 nm-10 um; 1.9 ng m/L to 1.9 ug/ mL ]), alone and in combination, on isolated mouse preantral follicle and human granulosa cell (hGC) cultures to study direct effects on follicle growth and ovarian steroidogenesis. Our results revealed that, in follicle culture, DEHP and BP attenuate estradiol output but only when present together. DEHP decreases progesterone concentrations in the spent media of hGC cultures, an effect that was attenuated when BP was added together with DEHP. Although changes in steroidogenesis were observed, no effects on follicular development or survival were noted in the culture systems. We suggest that BP and DEHP act with additive effect to decrease estradiol production whereas at later stages of follicle development BP blocks the effect of DEHP in hGCs resulting in decreased progesterone output. Taken together our results suggest that DEHP and BP adversely affect steroidogenesis from the preantral stage onward and the effects of these chemicals are both stage-dependent and modified by co-exposure.
By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /4-Hydroxybenzoates (Parabens)/
After butylparaben is intravenously infused into the dog, nonhydrolyzed butylparaben is found in brain, spleen, and pancreas. In liver, kidney, and muscle, it is immediately hydrolyzed to p-hydroxybenzoic acid. Six hours after oral administration of 1.0 g/kg to dogs, the peak plasma concentration of free and total butyl paraben (15 and 141 ug/cu cm) is reached. After 48 hr, butylparaben is eliminated.
Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability of coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butylparaben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of hydrophilic paraben.
Intravenous (IV) injections at 50 mg/kg methylparaben, ethylparaben, propylparaben, or butylparaben were administered to groups of three or more fasted dogs. Similarly, these compounds were administered orally at a dose of 1.0 g/kg. Blood and urine were analyzed at predetermined intervals. Immediately following IV injection, very little ester remained in the blood. Metabolites were detectable in the blood up to 6 hr postinjection and 24 hr postingestion. Recovery of all esters but butylparaben ranged from 58 to 94% of the administered dose. Absorption was essentially complete. Recovery of butylparaben after oral administration was 40% and 48 after IV administration. The authors considered this finding a result of less effective hydrolysis of butylparaben. Dogs given 50 mg/kg were then killed and the distribution of esters and metabolites to organs was determined. Pure ester was recovered only in the brain, spleen, and pancreas. High concentrations of metabolites were detected in the liver and kidneys. With in vitro assays, it was found that esterases in the liver and kidneys of the dog were extremely efficient in hydrolyzing parabens --- complete hydrolysis after 3 minutes for all parabens except butylparaben, which took 30 to 60 minutes. No accumulation of parabens was observed in the tissues of dogs given orally 1 g/kg/day methylparaben or propylparaben for 1 year. The rate of urinary excretion of esters and metabolites in these dogs increased to such an extent that after 24 hr, 96 % of the dose was excreted in the urine. This is contrasted with dogs given a single dose of paraben in which the 96 % excretion level was not attained until 48 hr. When 10 % methylparaben or propylparaben in hydrophilic ointment was applied to the skin of a white rabbit for 48 h, esters and metabolites were not detected in the kidneys.
An Efficient and Selective Deprotecting Method for Methoxymethyl Ethers
摘要：
Methoxymethyl ethers were selectively deprotected to the corresponding phenols in high yields by CBr4 and PPh3 in aprotic solvent (CICH2CH2Cl) under slightly thermal reaction conditions.
The present application provides compounds of formula: Methods of using these compounds for killing bacterial growth and treating bacterial infections are also provided.
本申请提供了以下化合物的公式：还提供了使用这些化合物杀灭细菌生长和治疗细菌感染的方法。
[EN] PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PRMT5 CONTENANT UNE DIHYDRO- OU TÉTRAHYDRO-ISOQUINOLÉINE ET LEURS UTILISATIONS
申请人：EPIZYME INC
公开号：WO2014100730A1
公开（公告）日：2014-06-26
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
esterification. Comparing with previously reported homogeneous and heterogeneous catalysts, Zr‐MOF‐808‐P can promote the reaction for a wide range of primary, secondary and tertiary amides with n‐butanol as nucleophilic agent. Different alcohols have been employed in amide esterification with quantitative yields. Moreover, the catalyst acts as a heterogeneous catalyst and could be reused for at least five
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as modulators of alpha 1 antitrypsin and treating diseases associated with alpha antitrypsin, particularly liver diseases.
