Thiourea appears as white or off-white crystals or powder. Sinks and mixes with water. (USCG, 1999)
颜色/状态:
White solid which crystallizes in a rhombic bipyramidal structure
气味:
Odorless
味道:
Bitter
蒸汽压力:
1.41X10-7 mm Hg at 25 °C
分解:
When heated to decomposition it emits very toxic fumes of nitroxides and sulfoxides.
燃烧热:
Heat of combustion at constant volume is -1482.2 kJ/mol (-19.47 kJ/g), and at constant pressure -1485.6 kJ/mol (-19.52 kJ/g)
汽化热:
6.0034X10+7 J/kmol at 454.15 K (est)
表面张力:
1.0404X10-2 N/m at 454.15 K
聚合:
Acrylaldehyde is very reactive & will polymerize rapidly, accelerating to violence, in contact with strong acid or basic catalysts. ... Exposure to weakly acidic conditions (nitrous fumes, sulfur dioxide, carbon dioxide), some hydrolysable salts, or thiourea will also cause exothermic & violent polymerization.
解离常数:
pK-value not determinable according to OECD guideline no. 112 with the titration method at 24 °C (forms no OH or H ions)
When (35)sulfur labelled cmpd was given by ip injection to rats 98% of admin radioactivity appeared in urine within 48 hr after injection. Chromatography of the urine showed that major product was undegraded thiourea, with small quantities of inorganic sulfate (6.2%) & ethereal sulfate (5.9%).
Thiourea, phenylthiourea, and methimidazole perfused into rat liver stimulated the biliary efflux of oxidized glutathione without affecting the excretion of reduced glutathione into either the bile or the caval perfusate. The results are consistent with a model based on S-oxygenation of thiocarbamide to formamide sulfenates catalyzed exclusively by the flavin-containing monooxygenase. The resulting sulfenate is reduced by glutathione, yielding oxidized glutathione and the parent thiocarbamide. Rapid cellular oxidation of glutathione by this mechanism leads to biliary efflux of the disulfide.
Thiourea is oxidized by thyroid gland peroxidase in the presence of iodine or iodide and hydrogen peroxide to form formamidine disulfide (NH2(NH)CSSC(NH)NH2). Formamidine disulfide is unstable and decomposes at pH values above 3.0, forming cyanamide, elementary sulfur, and thiourea. It was shown in vitro and in vivo that both cyanamide and thiourea are inhibitors of thyroid peroxidase (Davidson et al., 1979).
IDENTIFICATION AND USE: Thiourea occurs as white, lustrous crystals or flaky solids. It is not registered for current pesticide 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. It has many uses including for photography and photocopying papers, organic synthesis of dyes, drugs, and hair preparations, rubber accelerators, analytical reagents, amino resins, mold inhibitors, flame retardants for textiles, peptizing agents, pesticides, chelating agents, and as a reagent for bismuth and selenite ions. Other uses are as an additive for slurry explosives, as a viscosity stabilizer for polymer solutions (e.g., in drilling muds), and as a mobility buffer in petroleum extraction. The removal of mercury from wastewater from chlorine-alkali electrolysis and gold and silver extraction from minerals are also of economic importance. Thiourea has been identified as being used in hydraulic fracturing as a corrosion inhibitor. HUMAN EXPOSURE AND TOXICITY: The primary routes of potential human exposure to thiourea are inhalation and dermal contact. The greatest risk of potential exposure exists for workers involved in the production or use of thiourea. Thiourea has been identified as a sensitizer in people suffering from photosensitivity. It may also cause depression of bone marrow with anemia, leukopenia and thrombocytopenia. Thiourea was used in former times as a thyroid depressant in patients with hyperthyroidism. A daily dose of <15 mg (<0.2 mg/kg body weight per day for a 70-kg adult) in adults did not lead to measurable depression of the thyroid gland function, while a dose of 70 mg/day (about 1.0 mg/kg body weight per day) produced a remission of hyperthyroidism. ANIMAL STUDIES: Thiourea is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals. When administered in the drinking water, thiourea induced thyroid adenomas and carcinomas in rats of both sexes and squamous cell carcinomas of the Zymbal gland in male rats. When administered in the diet, thiourea induced hepatocellular adenomas in rats and hepatomas in rainbow trout. When injected intraperitoneally and administered in drinking water, thiourea induced squamous cell carcinomas and mixed cell sarcomas in the Zymbal gland of rats of both sexes. Thiourea also causes development and reproductive abnormalities. In studies with pregnant ewes administered 50 mg thiourea/kg body weight daily for 2, 4, or 6 months, abortion, stillbirth, birth of weak/low-weight lambs, dystokia, and retention of placenta were common features. The severity of changes was dependent upon the stage of gestation when hypothyroidism was induced. High dose thiourea severely inhibited thyroid function in rat pups, significantly depressed body growth, and retarded development of the acoustic startle response. At the low dose there was a significant reduction in growth, but no effect on acquisition of acoustic startle reflex. Thiourea has shown genotoxicity. When tested at a dose range of 1X10-2 to 1X10-5 M, was found to be weakly active in causing unscheduled DNA synthesis. In hepatocytes, thiourea elicited a linear increase in DNA repair replication in the concentration range tested (5-25 mM). In V79 cells, thiourea (10-40 mM) significantly increased the frequency of 8-azaguanine-resistant mutants. ECOTOXICITY: Treatment with 0.03% thiourea via immersion for 21 days induced hypothyroidism (thyroid hormone depletion) as evidenced by significantly reduced serum T(3) levels in the catfish, Clarias gariepinus. Thiourea-treated males had narrowed seminiferous lobules with fewer spermatozoa in testis, very little or no secretory fluid, reduced protein and sialic acid levels in seminal vesicles when compared to controls; accompanied by reduction in serum and tissue levels of testosterone (T) and 11-ketotestosterone (11-KT), a potent male specific androgen in fish. There were physiological and histological signs of recovery after 21 days such as reappearance of spermatozoa and partial restoration of 11-KT and T levels. In yearling rainbow trout, Salmo gairdneri, thiourea treatment resulted in depression of gill Na+/K+-ATPase activity in sea water (in 0.5% thiourea) or delayed adaptive increase in ATPase activity (in 0.3% thiourea) following sea water entry as compared to control fish.
The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated thiourea for carcinogenicity. According to their analysis, the weight-of-evidence for thiourea is group B2, which is based on sufficient evidence in animals. No data available in humans. As a group B2 chemical, thiourea is considered a probable human carcinogen..
Evaluation: There is inadequate evidence in humans for the carcinogenicity of thiourea. There is limited evidence in experimental animals for the carcinogenicity of thiourea. Overall evaluation: Thiourea is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
硫脲:合理预期为人类致癌物。
Thiourea: reasonably anticipated to be a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物:硫脲
IARC Carcinogenic Agent:Thiourea
来源:International Agency for Research on Cancer (IARC)
(35)S-Thiourea was shown to cross the placenta in mice and rats and to be preferentially stored in the thyroid gland, depending on the stage of development of this organ, where it affects iodine metabolism.
Pregnant mice were injected intravenously with 14C-labelled thiourea. Autoradiography revealed that radioactivity began to accumulate in the thyroid gland of mothers and fetuses after only 5 min and remained higher in this tissue than in any other organ during the entire 4-day observation period. Increased levels of radioactivity were also found in the walls of the large blood vessels, the cortex of the adrenal glands, the mammary glands, liver, lungs, and kidneys.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在大鼠中,静脉注射的[(14)C]硫脲在应用24小时后在肺、肝脏和肾脏蛋白质中均匀分布。
In rats, [(14)C]thiourea administered intravenously was found to be uniformly distributed in lung, liver, and kidney proteins 24 hr after application.
Thiourea is also absorbed to a lesser degree through the skin. Following dermal application of 2000 mg/kg body weight to rabbits in the form of an aqueous solution (26 mL of a 25% w/v solution), approximately 4% of the applied dose was found in the animals' urine; when applied in solid form, only 0.1% was found in the urine.
[EN] CRBN LIGANDS AND USES THEREOF<br/>[FR] LIGANDS CRBN ET LEURS UTILISATIONS
申请人:KYMERA THERAPEUTICS INC
公开号:WO2019140387A1
公开(公告)日:2019-07-18
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
本发明提供了化合物、其组合物以及使用这些化合物抑制CRBN并治疗CRBN介导的疾病的方法。
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人:AMGEN INC
公开号:WO2013123444A1
公开(公告)日:2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
Photoredox chemistry in the synthesis of 2-aminoazoles implicated in prebiotic nucleic acid synthesis
作者:Ziwei Liu、Long-Fei Wu、Andrew D. Bond、John D. Sutherland
DOI:10.1039/d0cc05752e
日期:——
Prebiotically plausible ferrocyanide–ferricyanide photoredox cycling oxidatively converts thiourea to cyanamide, whilst HCN is reductively homologated to intermediates which either react directly with the cyanamide giving 2-aminoazoles, or have the potential to do so upon loss of HCN from the system. Thiourea itself is produced by heating ammonium thiocyanate, a product of the reaction of HCN and hydrogen
NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
申请人:Ryono Denis E.
公开号:US20080009465A1
公开(公告)日:2008-01-10
Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure
wherein
is a heteroaryl ring;
R
4
is —(CH
2
)
n
-Z-(CH
2
)
m
—PO(OR
7
)(OR
8
), —(CH
2
)
n
Z-(CH
2
)
m
—PO(OR
7
)R
g
, —(CH
2
)
n
-Z-(CH
2
)
m
—OPO(OR
7
)R
g
, —(CH
2
)
n
Z—(CH
2
)
m
—OPO(R
9
)(R
10
), or —(CH
2
)
n
Z—(CH
2
)
m
—PO(R
9
)(R
10
);
R
5
and R
6
are independently selected from H, alkyl and halogen;
Y is R
7
(CH
2
)
s
or is absent; and
X, n, Z, m, R
4
, R
5
, R
6
, R
7
, and s are as defined herein; or a pharmaceutically acceptable salt thereof.
A method for treating diabetes and related diseases employing the above compounds is also provided.
提供了磷酸酯和磷酸酯激活剂,因此在治疗糖尿病和相关疾病方面非常有用,并具有以下结构:
其中
是杂环芳基环;
R
4
为—(CH
2
)
n
-Z-(CH
2
)
m
—PO(OR
7
)(OR
8
)、—(CH
2
)
n
Z-(CH
2
)
m
—PO(OR
7
)R
g
、—(CH
2
)
n
-Z-(CH
2
)
m
—OPO(OR
7
)R
g
、—(CH
2
)
n
Z—(CH
2
)
m
—OPO(R
9
)(R
10)
或—(CH
2
)
n
Z—(CH
2
)
m
—PO(R
9
)(R
10)
;
R
5
和R
6
分别选择自H、烷基和卤素;
Y为R
7
(CH
2
)
s
或不存在;以及
X、n、Z、m、R
4
、R
5
、R
6
、R
7
和s如本文所定义;或其药用盐。
还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes
申请人:Metabasis Therapeutics, Inc.
公开号:US06756360B1
公开(公告)日:2004-06-29
Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.