1-bromopropane appears as a colorless liquid. Slightly denser than water and slightly soluble in water. Flash point below 75°F. When heated to high temperatures may emit toxic fumes.
颜色/状态：
Colorless liquid
气味：
Sweet odor
蒸汽密度：
4.25 (Air = 1)
蒸汽压力：
110.8 mm Hg at 20 °C
大气OH速率常数：
1.18e-12 cm3/molecule*sec
稳定性/保质期：
Stable under recommended storage conditions.
自燃温度：
914 °F (490 °C)
分解：
Hazardous decomposition products formed under fire conditions - Carbon oxides, hydrogen bromide gas.
... Six workers, 1 male and 5 female, were exposed to high ambient 1-Bromopropane (1-BP) concentrations while employed in a golf club cleaning factory. 1-BP was identified in the bulk solvent sample used by the workers and confirmed the workers' daily occupational exposure to 1-BP for 3-10 months. The major presenting symptoms were tingling pain, soreness in lower extremities, and paresthesia. N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), a 1-BP metabolite, was identified by LC/MS/MS in the urine (0.171-1.74 mg/g-Cr) of these workers 5-26 days following 1-BP exposure. ...
... In this study, the factors influencing the disposition and biotransformation of 1-bromopropane (1-BrP) were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). (1,2,3-(13)C)1-BrP and (1-(14)C)1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. ... Metabolites characterized in urine of rats and mice include N-acetyl-S-propylcysteine, N-acetyl-3-(propylsulfinyl)alanine, N-acetyl-S-(2-hydroxypropyl)cysteine, 1-bromo-2-hydroxypropane-O-glucuronide, N-acetyl-S-(2-oxopropyl)cysteine, and N-acetyl-3-[(2-oxopropyl)sulfinyl]alanine. These metabolites may be formed following oxidation of 1-bromopropane to 1-bromo-2-propanol and bromoacetone and following subsequent glutathione conjugation with either of these compounds. ...
Three metabolites of 1-bromopropane (1-BP) were measured in urine samples collected from 30 workers exposed to 1-BP at two facilities making furniture seat cushions and evaluated for use as biomarkers of exposure. The mercapturic acid metabolite, N-acetyl-S-(n-propyl)-l-cysteine (AcPrCys), 3-bromopropionic acid (3-BPA), and bromide ion levels (Br(-)) were quantitated for this evaluation. ...
Glutathione S-alkyl transferase catalyzes the conjugation of alkyl halides and nitroalkanes in which halogen or nitro group is replaced. Further metabolism of conjugates of this group to alkylmercapturic acid sulfoxides has been reported for...1-bromopropane.
1-bromopropane is metabolized rapidly in the liver. Three mercapturic acids are produced: N-acetyl-S-propyl cysteine, N-acetyl-S-propyl cysteine-S-oxide and N-acetyl-S-(2-hydroxypropyl)cysteine. 1-bromopropoane also reacts rapidly with glutathione and can form glutathione conjugates.
IDENTIFICATION AND USE: 1-Bromopropane (1-BP) is a colorless liquid. 1-BP is used primarily as a solvent cleaner in vapor and immersion degreasing operations to clean optics, electronics, and metals and as a solvent vehicle in industries using aerosol-applied adhesives, such as foam cushion manufacturing. HUMAN STUDIES: Occupational exposure to 1-BP has been linked to neurological illnesses. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system. A 43-year-old male industrial worker developed muscle weakness, pain, numbness, and gait disturbance. Neurological examination indicated sensory ataxic neuropathy associated with mild impairment of upper motor neurons. He had used 1-BP as a cleaning agent for metal parts at his workplace without appropriate protection. Another case study reported that a 19-year-old male experienced weakness of the lower extremities and the right hand, numbness, and difficulty swallowing and urinating after 2 months of occupational exposure to a degreasing solvent based on 1-BP. 1-BP is cytotoxic but not corrosive, based on results from a cultured reconstructed human epidermal model (EpiDerm Skin Corrosivity Test). 1-BP can induce DNA damage in vitro in human leukocytes. ANIMAL STUDIES: 1-BP did not produce cutaneous reactions in guinea pigs attributable to skin sensitization. Inhalation exposure to 1-BP caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1-BP, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. It is unclear whether induction of immunotoxicity by 1-BP plays a role in tumor development. 1-BP caused immunosuppression in rodents. In particular, it reduced the numbers of T cells and T-cell subpopulations. In addition, there is evidence that 1-BP caused an inflammatory response. In rats, exposure to 1-BP did not affect memory function or motor coordination but muscle strength decreased dose-dependently. Dose-dependent increases in spontaneous locomotor activity and open-field behavior indicated that 1-BP has excitatory effects on the CNS of male rats. Rats exposed at 1000 and 1500 ppm 1-BP for 4 to 7 weeks exhibited decreases in body weight and motor nerve conduction velocities, increased distal latency of peripheral nerves, and neuronal dysfunction in the dentate gyrus of the brain. In two-generation study, 7-week-old rats were exposed 6 hours/day, 7 days/week for 70 days prior to mating at 0, 100, 250, 500, or 750 ppm 1-BP. Females were not exposed on postnatal day 0 to 4 and only they, not their litters, were exposed during postnatal days 5 to 21. F1 rats began direct exposure at weaning. Dose-related increases in estrous cycle length at >/=250 ppm, and follicular cysts and interstitial hyperplasia of ovaries at 500 ppm were observed in F0 and F1 females. Reduced fertility and litter size was observed in the F0 and F1 generations at >/=250 ppm. Prenatal 1-BP exposure in dams can cause delayed adverse effects on excitability of pyramidal cells in the hippocampal CA1 subfield of offspring. 1-BP was mutagenic with or without metabolic activation toward Salmonella typhimurium tester strains TA1535 and TA100 when tested in a closed system, but it was not mutagenic toward strains TA1537, TA1538, or TA98. However in other studies, 1-BP was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with and without metabolic activation. Bacterial strains tested included Salmonella typhimurium strains TA97, TA98, TA100, and TA1535, and Escherichia coli strain WP2 uvrA/pKM101. 1-BP was not mutagenic in vivo when tested in mice and rats.
Organobromide compounds, especially alkylbromides are strong alkylating agents. Consequently they can randomly modify the surfaces of proteins and lipids, leading to the disruption of enzyme, transporter or membrane functions. Alkylation of DNA by alkylbromides may also lead to mutations. 1-bromopropane reacts quickly with hepatic glutathione (GSH) leading to its rapid depletion and subsequent liver damage. Long-term exposure to 1-bromopropane decreases neurogenesis in the dentate gyrus which may contribute to the neurotoxicity. Downregulation of brain derived neurotrophic factor and glucocoritoid receptor mRNA expression and low hippocampal norepinephrine levels might contribute, at least in part, to the reduced neurogenesis.
1-Bromopropane is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3：已确认的动物致癌物，对人类的相关性未知。
A3: Confirmed animal carcinogen with unknown relevance to humans.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of 1-bromopropane. There is sufficient evidence in experimental animals for the carcinogenicity of 1-bromopropane. Overall evaluation: 1-Bromopropane is possibly carcinogenic to humans (Group 2B).
... In this study, the factors influencing the disposition and biotransformation of 1-bromopropane (1-BrP) were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). (1,2,3-(13)C)1-BrP and (1-(14)C)1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO(2), urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or (14)CO(2) (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid ( approximately 50%) and high ( approximately 71%) dose groups; while the percentage of the dose exhaled as (14)CO(2) decreased (19 to 10%). The molar ratio of exhaled (14)CO(2) to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. ((14)C)1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (<2%), or retained in the tissues and carcass (<6%) of rats and mice administered i.v. 5 to 100 mg/kg ((14)C)1-BrP. ... Rats pretreated with 1-aminobenzotriazole (ABT), a potent inhibitor of P450 excreted less in urine (down 30%), exhaled as (14)CO2 (down 80%), or retained in liver (down 90%), with a concomitant increase in radioactivity expired as VOC (up 52%). Following ABT pretreatment, rat urinary metabolites were reduced in number from 10 to 1, N-acetyl-S-propylcysteine, which accounted for >90% of the total urinary radioactivity in ABT pretreated rats. Together, these data demonstrate a role for cytochrome P450 and glutathione in the dose-dependent metabolism and disposition of 1-BrP in the rat.
/Investigators/ injected Sprague-Dawley rats intraperitoneally with 200 mg/kg 1-BP and observed a rapid excretion of greater than half of the administered dose in expired air. By hour 100, 25% of the 1-BP dose was excreted in the urine.
3-丁基吡啶g甲基丙烯酸单丁酯，二乙基己酸酯和二甲苯，可用于定性和定量分析。Unter den monomethylierierten Produkten herrscht das 3-Butyl-2-methyl-pyridin vor; 3-丁基-4-甲基-和5-丁基-2-甲基-吡啶 3-丁基-5-甲基-吡啶表示kaum。Die Konstitution des 3-Butyl-4-methyl-pyridins wurde durch Abbau zumγ-Picolin bewiesen。芦苇形式的3-丁-二甲基-吡啶异丁烯的芳烃衍生物。和二苯并呋喃酮和3-丁基-2,6-二甲基-吡啶二烷。
2-Amino-6-arylsulfonylbenzonitriles as Non-nucleoside Reverse Transcriptase Inhibitors of HIV-1
作者：Joseph H. Chan、Jean S. Hong、Robert N. Hunter、G. Faye Orr、Jill R. Cowan、Douglas B. Sherman、Steven M. Sparks、Barbara E. Reitter、C. Webster Andrews、Richard J. Hazen、Marty St Clair、Lawrence R. Boone、Rob G. Ferris、Katrina L. Creech、Grace B. Roberts、Steven A. Short、Kurt Weaver、Ronda J. Ott、Jingshan Ren、Andrew Hopkins、David I. Stuart、David K. Stammers
DOI：10.1021/jm0004906
日期：2001.6.1
A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship
Imidazoline derivatives as alpha-1A adrenoceptor ligands
申请人：Bigham Eric Cleveland
公开号：US06884801B1
公开（公告）日：2005-04-26
Compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof are disclosed. Such compounds are useful in the treatment of Alpha-1A mediated diseases or conditions such as urinary incontinence.
