Glycidol is rapidly hydrolyzed to glycerol (97.2%) and alpha-chlorohydrin (3-chloro-1,2-propanediol, 2.8%) in 0.1 M hydrochloric acid, with a half-life of 10 min. At pH 7 or 8, glycidol readily reacts with glutathione to form S-(2,3-dihydroxypropyl)glutathione.
S-(2,3-Dihydroxypropyl)glutathione, S-(2,3-dihydroxypropyl)cysteine and beta-chlorolactic acid are the major metabolites isolated from rat urine after intraperitoneal administration of glycidol. The generation of beta-chlorolactic acid is presumably a result of initial formation of alpha-chlorohydrin, with subsequent oxidation by alcohol and aldehyde dehydrogenases. Glycidol is hydrolyzed to glycerol by rat liver microsomal preparations.
来源:Hazardous Substances Data Bank (HSDB)
代谢
肝脏环氧水合酶将环氧丙醇转化为甘油。环氧丙醇是肺和肝脏细胞质谷胱甘肽S-转移酶的底物。
Liver epoxide hydrase converted glycidol to glycerol. Glycidol was a substrate for lung and liver cytosolic glutathione S-transferases.
... The DNA damaging effects of 3-MCPD and its metabolites, glycidol and beta-chlorolactic acid, /were also studied/ in the in vitro comet assay on CHO cells. /The/ results show the absence of genotoxic potential of 3-MCPD in vivo in the target as well as in the non-target organs. Glycidol, the epoxide metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in vitro in mammalian cells.
No epidemiological data relevant to the carcinogenicity of glycidol were available. There is sufficient evidence in experimental animals for the carcinogenicity of glycidol. Overall evaluation: Glycidol is probably carcinogenic to humans (Group 2A).
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.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
环氧醇：有理由预期为人类致癌物。
Glycidol: 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：缩水甘油
IARC Carcinogenic Agent:Glycidol
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：2A组：可能对人类致癌
IARC Carcinogenic Classes:Group 2A: Probably carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
The comparative disposition of glycidol was investigated in rats following oral (po) or intravenous (iv) administration at doses of 37.5 and 75 mg/kg. These were the doses used in the National Toxicology Program (NTP) oncogenicity study with glycidol. Approximately 87-92% of the dose was absorbed from the gastrointestinal tract of the rat. (14)C-Glycidol equivalents were eliminated in urine (40-48% of dose in 72 hr), feces (5-12%), and exhaled as CO2 (26-32%). At both doses, 9-12% and 7-8% (estimated) of the dose remained in tissues at 24 and 72 hr following dosing, respectively. In general, the concentrations of glycidol equivalents in tissues were proportional to the dose. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney, and spleen, and the lowest in adipose tissue, skeletal muscle, and plasma. The pattern of distribution of radioactivity in tissues was similar for both the iv and po routes. The total recovery of radioactivity ranged from 87 to 91% of dose. Urinary radioactivity was resolved by high-performance liquid chromatography (HPLC) analysis into 15 metabolites. There were one major (14-21% of the dose) and four lesser metabolites (each representing 2-8%); the others were minor, each representing 1% or less of the dose. In general, the urinary metabolic profile was similar following either iv or po administration at the two doses studied. Previous studies by other investigators suggested that alpha-chlorohydrin, which was presumably formed from glycidol by the HCl in the stomach, was metabolized and excreted in urine as beta-chlorolactic acid. The results of the present study show that very little, if any, urinary radioactivity coeluted with authentic beta-chlorolactic acid following either iv or po administration. Therefore, it is concluded that the conversion of glycidol to alpha-chlorohydrin is quantitatively insignificant. However, it may be significant with regard to glycidol reproductive toxicity. Also, the NTP oncogenicity study with glycidol was carried out within the dose range in which its disposition characteristics were linear.
Approximately 87-92% of 37.5 or 75 mg/kg body weight (bw) orally administered glycidol is absorbed from the gastrointestinal tract of male Fischer 344 rats. Seven to eight per cent of the dose remained in tissues 72 hr following administration. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney and spleen.
通过新颖的开环硝化反应，使十八种各种环氧化合物与N 2 O 5在氯化烃溶剂（主要为CH 2 Cl 2）中反应，得到邻位硝酸酯产物。与传统的混合酸硝化方法相比，该方法提供了更轻松的温度控制和更简单的分离步骤。它还可以在多官能底物上进行选择性硝化反应。讨论了反应的范围和局限性，以及利用N 2 O 4与硝酸亚硝酸酯原位进行原位氧化的替代方法的范围和局限性。
Curcumin derivatives with improved physicochemical properties and nanoliposomes surface-decorated with the derivatives with very high affinity for amyloid-beta1-42 peptide
申请人：Niaraki, Anna
公开号：EP2436673A1
公开（公告）日：2012-04-04
Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets Aβ plaques and interferes with their formation, suggesting a potential role for prevention or treatment of AD. In the present invention, curcumin-derivatives with improved physicochemical properties were synthesized and a "click chemistry" as well as a conventional liposome preparation method, were used to generate nanoliposomes decorated with the curcumin derivatives. These derivatives were designed to maintain the planar structure required for interaction with Aβ, as directly confirmed by Surface Plasmon Resonance experiments. Surface Plasmon Resonance experiments, measuring the binding of flowing liposomes to immobilized Aβ1-42, indicated that the liposomes exposing curcumin derivatives have extremely high affinity for Aβ1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions. The present invention describes the synthesis of the curcumin derivatives and the preparation and characterization of new nanoliposomes with a very high affinity for Aβ1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.
A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Said method is effective when provided in addition to standard therapies, notably chemotherapy using cytotoxic drugs and other forms of immune therapy including therapeutic vaccines.
[EN] HETEROARYL SUBSTITUTED AMINOPYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS D'AMINOPYRIDINE SUBSTITUÉS PAR HÉTÉROARYLE
申请人：BRISTOL MYERS SQUIBB CO
公开号：WO2016210034A1
公开（公告）日：2016-12-29
Disclosed are compounds of Formula (I) or salts thereof, wherein HET is a heteroaryl selected from pyrrolo[2,3 b]pyridinyl, pyrrolo[2,3 d]pyrimidinyl, pyrazolo[3,4 b]pyridinyl, pyrazolo[3,4 d]pyrimidinyl, imidazolo[4,5 b]pyridinyl, and imidazolo[4,5 d]pyrimidinyl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a nitrogen ring atom in said heteroaryl and wherein said heteroaryl is substituted with zero to 2 Rb; A is pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxadiazolyl or dihydroisoxazolyl, each substituted with zero or 1 Ra; and R3, Ra, and Rb are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.
Glycerol as a source of designer solvents: physicochemical properties of low melting mixtures containing glycerol ethers and ammonium salts
作者：Alejandro Leal-Duaso、Pascual Pérez、José A. Mayoral、Elisabet Pires、José I. García
DOI：10.1039/c7cp04987k
日期：——
In this work we report the preparation of mixtures of several alkyl glyceryl ethers, as hydrogen bond donor compounds, with two ammonium salts, choline chloride and N,N,N-triethyl-2,3-dihydroxypropan-1-aminium chloride. The stability of the mixtures at different molar ratios and temperatures has been evaluated in order to determine the formation of lowmelting mixtures. Liquid and stable mixtures have
Sulfamate esters of the formula (HO).sub.p --A--[OSO.sub.2 NR.sup.1 R.sup.2 ].sub.z where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O).sub.2 NR.sup.1 R.sup.2 groups attached to carbons of the alkyl moiety and is always at least one; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.
