NIOSH REL: TWA 0.3 mg/m3, IDLH 100 mg/m3; OSHA PEL: TWA
0.3 mg/m3
物理描述：
Antu appears as white crystal or powder; technical product is gray powder. Has no odor but a bitter taste. Used primarily as a rodenticide for control of adult Norway rats. Not produced commercially in the U.S. (EPA, 1998)
颜色/状态：
Prisms from alcohol
气味：
Odorless
味道：
Bitter taste
闪点：
May burn but will not ignite readily (EPA, 1998)
蒸汽密度：
6.99 (EPA, 1998) (Relative to Air)
蒸汽压力：
1.1X10-6 mm Hg at 25 °C (est)
稳定性/保质期：
Stable on exposure to air and to sunlight.
分解：
Hazardous decomposition products include: sulfur dioxide, oxides of nitrogen, and carbon monoxide.
ANTU is metabolized by rat liver and lung microsomes to alpha-naphthylurea (anu) and atomic sulfur. ANTU pulmonary toxicity may result, in part, from covalent binding of sulfur /SRP: or a metabolite containing carbonyl carbon of ANTU to macromolecules of liver and lung microsomes/.
...The covalent binding of atomic sulfur released in the cytochrome P-450 monooxygenase-catalyzed metabolism of thiono-sulfur compounds is responsible for monooxygenase activity being inhibited. Damage to liver and possibly lung edema and neoplasia result from the covalent binding of the electrophilic S-oxides, S-dioxides or carbene derivatives of these S-oxides and S-dioxides to tissue macromolecules.
The in vivo administration of the radiolabeled lung toxin alpha-naphthylthiourea (ANTU) to rats leads to the covalent binding of radioactivity to the macromolecules of the lung and liver. Very little radioactivity is bound in these organs when an equal amount of the (14)C-labeled oxygen analog of ANTU, (14)C-alpha-naphthylurea (ANU), is administered. ANU is essentially nontoxic to rats. ANTU is metabolized in vitro by lung and liver microsomes to an intermediate which covalently binds to the macromolecules of the microsomes. This covalent binding, which requires NADPH, leads to a decrease in mixed-function oxidase activity and to a decrease in the level of cytochrome P-450 detectable as its CO complex. Incubation of microsomes with ANTU in the absence of NADPH or with ANU in the presence of NADPH, has no effect on these parameters. Pretreatment of rats with small nonlethal doses of ANTU daily for 5 days brings about a decrease in the activity of the mixed-function oxidase enzyme system in the lung which metabolizes parathion. In addition, this pretreatment decreases the toxicity of ANTU and leads to a decrease in the amount of radioactivity bound to the macromolecules of the lung when the animals are given a lethal dose of (35)S-ANTU.
The in vitro metabolism of the lung toxin alpha-naphthylthiourea (ANTU) was examined using [(35)S] and [(14)C] ANTU and microsomes isolated from the liver and lung of phenobarbital-treated rats. ANTU was metabolized by this system to alpha-naphthylurea (ANU). A portion of the sulfur released in this reaction binds covalently to microsomal proteins. The Km values for the formation of ANU using the liver and lung microsomal system were 4.56 and 4.18 mM, respectively. The metabolism of ANTU to ANU required NADPH for optimum activity and was inhibited by carbon monoxide and anerobic conditions. The reaction was also inhibited in the presence of an antibody to rat liver cytochrome P450. A portion of the sulfur released during the oxidative desulfuration of [(35)S] ANTU to ANU was shown to react with the sulfhydryl group of cysteine residues in the microsomal proteins to form a hydrodisulfide.
IDENTIFICATION AND USE: Alpha-Naphthyl thiourea (ANTU) is a white, crystalline, or gray odorless powder with a bitter taste. It was first used as a rodenticide for the control of adult Norway rats. It was widely used in the 1940s but has subsequently been replaced by other compounds in most countries including the U.S. It is not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: ANTU is well absorbed by skin contact and inhalation. Oral ingestion may result in vomiting, shortness of breath, bluish discoloration of the skin, pulmonary edema or liver injury. Repeat exposures can injure the thyroid and adrenals, producing hypothyroidism. ANIMAL STUDIES: Oral feeding of ANTU to rats at 10 mg/kg body weight increased the blood glucose levels by 100% after 22 hours. Acute exposure also caused elevated plasma activities of aspartate and alanine aminotransferases and increased the activity of the lactate dehydrogenase 5 (LD5) isoenzyme, suggesting that the liver is one of the targets in poisoning in ANTU-treated rats. Toxic symptoms observed in laboratory animals given repeated doses of alpha-naphthyl thiourea include impaired weight gain and deformities of the legs and feet; inhibition of hair growth and defective hair pigmentation; thyroid hyperplasia and hypercholesterolemia; and fatty degeneration of the liver and bile-duct proliferation. Other effects that have been reported are inhibition of pulmonary aniline hydroxylase activity, increased pulmonary aminopyrine demethylase activity and inhibition of Na+/K+ ATPases in erythrocyte membranes and kidney microsomes. Microsomes from rat liver and lung release atomic sulfur from alpha-naphthyl thiourea. Pulmonary toxicity may result, at least in part, from binding of atomic sulfur to tissue macromolecules in susceptable species. ANTU is mutagenic when metabolized by liver microsomal fractions from rats treated with either Aroclor 1254 or phenobarbital. It also transforms hamster embryo cells in an in vitro carcinogenesis bioassay.
EVALUATION: The available data were inadequate to evaluate the carcinogenicity of 1-naphthylthiourea to exptl animals. No data on humans were avail. The avail data are insufficient to evaluate the carcinogenicity of 1-naphthylthiourea to humans.
.../Detected in tissues only if material has/ been obtained within 24 hr of ingestion of a fairly large quantity of ANTU. The results of chemical examination of tissues for ANTU are uniformly negative in cases where the animals have survived for more than 24 hours.
Twenty hr after oral admin of 10 mg/kg of ANTU to albino rats, 40% was excreted in urine and less than 1% in feces. Approx 36% of urinary ANTU was excreted in the original form, and the rest in 3 metabolites.
Max ANTU content reached in rat pleural effusion, lung, skeletal muscles, and pancreas 4 hr after oral administration of 10 mg/kg. Albumin contained 80% of ANTU present in serum and pleural effusion.
Absorption of 1-naphthylthiourea from the gut is rapid, especially in the presence of fat. Differences between oral and parenteral LD50 values suggest that gut absorption of this compound may be incomplete in some species.
bisthiazole derivatives represent a prevalent scaffold in the antimicrobial drug discovery. Therefore, we have decided to synthesize somenew series of 4,5′‐bisthiazoles. A total of 17 compounds were synthesized, their structural elucidation being based on elemental analysis (C,H,N,S) and spectroscopic data (MS and 1H NMR). Their in vitro antimicrobial activities were assessed against several Gram‐positive
噻唑和联噻唑衍生物代表了抗菌药物发现中的普遍支架。因此，我们决定合成一些新的4,5'-双噻唑系列。总共合成了17种化合物，其结构解析基于元素分析（C，H，N，S）和光谱数据（MS和1 H NMR）。使用分光光度法评估了它们对几种革兰氏阳性和革兰氏阴性细菌菌株以及一种真菌菌株（白色念珠菌）的体外抗菌活性。一些化合物对革兰氏阴性大肠杆菌，鼠伤寒沙门氏菌和革兰氏阳性菌表现出中等至良好的抗菌活性。金黄色葡萄球菌和蜡状芽孢杆菌菌株。所有合成的化合物对白念珠菌均具有中度到很好的抑菌活性。
Synthesis and Evaluation of the 2-Aminothiazoles as Anti-Tubercular Agents
作者：Edward A. Kesicki、Mai A. Bailey、Yulia Ovechkina、Julie V. Early、Torey Alling、Julie Bowman、Edison S. Zuniga、Suryakanta Dalai、Naresh Kumar、Thierry Masquelin、Philip A. Hipskind、Joshua O. Odingo、Tanya Parish
DOI：10.1371/journal.pone.0155209
日期：——
designing and synthesizing a large number of analogs and testing these for activity against M. tuberculosis, as well as eukaryotic cells. We determined that the C-2 position of the thiazole can accommodate a range of lipophilic substitutions, while both the C-4 position and the thiazole core are sensitive to change. The series has good activity against M. tuberculosis growth with sub-micromolar minimum
PHYTOSANITARY COMPOSITIONS COMPRISING AN ETHER-AMIDE COMPOUND
申请人：RHODIA OPERATIONS
公开号：US20150208645A1
公开（公告）日：2015-07-30
The object of the present invention is phytosanitary compositions comprising an active phytosanitary product and an ether-amide compound. The ether-amide compound may natively be present as a solvent, co-solvent, crystallization inhibitor or an agent for increasing bioactivity of the active phytosanitary product.
A one-pot preparation of cyanamide from dithiocarbamate using molecular iodine
作者：Jayashree Nath、Bhisma K. Patel、Latonglila Jamir、Upasana Bora Sinha、K. V. V. V. Satyanarayana
DOI：10.1039/b914283p
日期：——
method for the synthesis of cyanamides from dithiocarbamate salts via a double desulfurization strategy using molecular iodine is disclosed. Dithiocarbamates, by the action of iodine yield isothiocyanates in situ, which on treatment with aqueous NH3 give thioureas. The thioureas so generated undergo further oxidative desulfurization with I2 giving corresponding cyanamides in good yields. Environmental
[EN] HINDERED DISULFIDE DRUG CONJUGATES<br/>[FR] CONJUGUÉS MÉDICAMENTEUX À PONT DISULFURE ENCOMBRÉ
申请人：GENENTECH INC
公开号：WO2017064675A1
公开（公告）日：2017-04-20
The invention relates generally to disulfide drug conjugates wherein a linker comprising a sulfur-bearing carbon atom substituted with at least one hydrocarbyl or substituted hydrocarbyl is conjugated by a disulfide bond to a cysteine sulfur atom of a targeting carrier, and wherein the linker is further conjugated to a drug moiety. The invention further relates to activated linker-drug conjugates suitable for conjugation to a targeting carrier by a disulfide bond. The invention further relates to methods for preparing hindered disulfide drug conjugates.
