Neurotoxin - Other CNS neurotoxin
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.
Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Xylitol was investigated for its ability to ameliorate hemolytic anemia induced by acetylphenylhydrazine in rabbits. Animal experiments were performed using two different concentrations of xylitol, a 5% and a 10% solution with a total dose of 2 g/kg bw and infusion rates of 10 mg and 20 mg xylitol/kg bw/min respectively. Two doses of acetylphenylhydrazine (APH), 5 and 10 mg/kg, were injected ip as hemolytic inducers in different groups of rabbits. All the rabbits infused with xylitol showed significantly less acute APH-induced hemolysis. The isotonic 5% xylitol solution was found to maintain and restore the hematological parameters (packed cell volume, hemoglobin concentration, reduced glutathione (GSH) content, and reticulocyte counts) better than the 10% xylitol solution. Increased 51CR-red cell survival confirmed the beneficial effect of xylitol. The survival of erythrocytes as represented by chromium-labeling in rabbits infused with 5% xylitol after treatment with 10 mg/kg APH increased from about 33% (the survival of red cells in rabbits injected with APH alone) to 67% of normal rabbits' red cell survival. Erythrocytes in APH-treated animals took up xylitol more readily than erythrocytes from control animals.
One millimolar ascorbic acid and alpha-mercaptopropionylglycine significantly (p<0.005) protected against RBC Heinz body formation during incubation with acetylphenylhydrazine, while cysteine, cysteamine, and methionine did not. The effect of ascorbic acid was concentration dependent with concentrations as low as 0.1 mM having significant antioxidant effects.
The effect of pteroyl glutamate (PGA) on the distribution of folates during hemolysis induced by acetyl-phenylhydrazine (APH) was investigated. One group of rabbits received daily APH injections, 1 mL of a 2.5% solution/kg; another group received 3 injections each of 10 mg PGA in addition to APH. Blood samples were collected for blood count and folate activity determinations. Animals were killed on day 8, and bone marrow and liver were analyzed for folate activity by 3 different bioassays. Packed red blood cells were incubated with radio labeled PGA to measure uptake. As reticulocytosis due to APH increased to 87% on day 7, there was a gradual rise in red blood cell folate activity. Serum folate activities were normal, liver activities were somewhat depressed, and bone marrow folate activity was elevated compared to untreated controls. When rabbits were treated with PGA as well, folate activity was 2-5 fold higher, and its rise more pronounced in 2 of 3 bioassays, but not when determined with Pediococcus-cerevisiae. Similar results were seen when serum folate activity was measured. All 3 bioassays showed an increase in folate with APH and PGA compared to APH alone, while with liver folate there was significant difference between the two control groups. The mean uptake of labeled PGA by packed red blood cells was 2.7% of folates present in the incubation when rabbits were treated with APH alone, and 0.72% when they were given both APH and PGA. /It was concluded/ that while the hemolytic stimulus brings about a substantial transfer of folates from the bone marrow, the hemopoietic tissue can utilize more folate when additional amounts are made available by parenteral administration of PGA.
The reaction of oxyhemoglobin and acetylphenylhydrazine, which results in hemoglobin denaturation and precipitation, was found to be influenced by H202 and superoxide (O2-.) generated during the reaction. By analysing the different hemoglobin oxidation products, it was found that by influencing the rate at which oxyhemoglobin was oxidized, H2O2 accelerated the overall hemoglobin breakdown, and O2-. inhibited it. By adding GSH (reduced glutathione) or ascorbate, it was possible to slow down the rates of both oxyhemoglobin oxidation and O2-. production, and the overall rate of hemoglobin breakdown. These results are compatible with a mechanism involving production of the acetylphenylhydrazyl free radical, and with GSH, ascorbate and O2-. acting as radical scavengers and preventing its further reactions. The reaction produced choleglobin, as well as acetylphenyldiazine and methemoglobin, which combined to form a hemichrome. The hemichrome was less stable and precipitated first. It was also less stable than the hemichrome formed by direct reaction of acetylphenyldiazine with methemoglobin, and it is proposed that this is because the methemoglobin produced from oxyhemoglobin and acetylphenylhydrazine was modified by the free radicals and H2O2 produced in the reaction.
Synthesis and Biological Evaluation of the 1-Arylpyrazole Class of σ<sub>1</sub> Receptor Antagonists: Identification of 4-{2-[5-Methyl-1-(naphthalen-2-yl)-1<i>H</i>-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862)
作者：José Luis Díaz、Rosa Cuberes、Joana Berrocal、Montserrat Contijoch、Ute Christmann、Ariadna Fernández、Adriana Port、Jörg Holenz、Helmut Buschmann、Christian Laggner、Maria Teresa Serafini、Javier Burgueño、Daniel Zamanillo、Manuel Merlos、José Miguel Vela、Carmen Almansa
DOI：10.1021/jm3007323
日期：2012.10.11
yl}morpholine (S1RA, E-52862), which showed high activity in the mouse capsaicin model of neurogenicpain, emerged as the most interesting candidate. In addition, compound 28 exerted dose-dependent antinociceptive effects in several neuropathic pain models. This, together with its good physicochemical, safety, and ADME properties, led compound 28 to be selected as clinical candidate.
Novel 2,3,5-trisubstituted-1,2,3,5-thiatriazolidin-4-one-2-oxides have been found to have herbicidal activity. These 1,2,3,5-thiatriazolidin-4-one-2-oxides are prepared by reacting an N-aminourea (semicarbazide) and thionyl chloride.
Formation of Enehydrazine Intermediates through Coupling of Phenylhydrazines with Vinyl Halides: Entry into the Fischer Indole Synthesis
作者：Fuxu Zhan、Guangxin Liang
DOI：10.1002/anie.201207173
日期：2013.1.21
Cut to the chase: Direct formation of an enehydrazine, an intermediate in the classic Fischerindolesynthesis, solves the regioselectivity problem associated with indolization. This approach not only achieves selective synthesis of indoles through proper selection of the vinyl halide, but also leads to quick construction of desoxyeseroline and esermethole, as well as the key structural motif in the
[EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
申请人：BIOGEN IDEC INC
公开号：WO2011029046A1
公开（公告）日：2011-03-10
The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.
本发明提供了用作Btk抑制剂的化合物、其组合物以及使用方法。
Synthesis of 1,3,4-oxadiazolium and 1,3,4-oxadiazolo[3,2-a]pyridinium salts
作者：G. V. Boyd、S. R. Dando
DOI：10.1039/j39700001397
日期：——
is described. Numerous 3-aryl-1,3,4-oxadiazolium salts, containing a novel type of heterocyclic cation, have been prepared by the action of carboxylic anhydrides on diacylarylhydrazines in the presence of perchloric or fluoroboric acid. 1,3,4-Oxadiazolo[3,2-a]pyridinium salts are similarly formed from 1 -acylamino-2-pyridones. The stability of the salts and their i.r. and n.m.r. spectra are discussed
已经研究了一些简单的1,3,4-恶二唑的质子化和烷基化，并描述了一种新的1,3,4-恶二唑的合成。在高氯酸或氟硼酸的存在下，通过羧酸酐对二酰基芳基肼的作用，已经制备了许多含有新型杂环阳离子的3-芳基-1,3,4-恶二唑鎓盐。类似地由1-酰基氨基-2-吡啶酮形成1,3,4-氧杂二唑[3,2- a ]吡啶鎓盐。讨论了盐的稳定性及其ir和nmr光谱。
