14C-labeled 2-nitropropane was administered to chimpanzees and rats, the 14C-labeled biotransformation metabolites were principally carbon dioxide, acetone and isopropanol. ... It has been postulated that N-nitro compounds and oxygen radicals are reactive intermediates in the denitrification of 2-nitropropane.
The enzymatic system oxidizing 2-nitropropane (2-NP) to acetone and nitrite was identified through in vitro experiments using microsomes isolated from mammalian liver. /It was/ determined that cytochrome P-450, in liver microsomes from phenobarbital-pretreated rats, bound 2-NP. /It was/ subsequently reported that liver microsomes from rats pretreated with phenobarbital or 3-methylcholanthrene rapidly catalysed the oxidation of 2-NP to acetone and nitrite. The latter were produced in roughly equal quantities. Surprisingly, however, the rate of this reaction was not diminished under conditions of reduced oxygen pressure. The activity of preparations from untreated control rats was generally very low. /It was/ demonstrated that this enzyme system in rats was active in metabolizing other aliphatic nitro compounds. ...Working with mice, /researchers/ obtained somewhat different results. They reported rapid denitrification of 2-NP to nitrite and acetone by liver microsomes from untreated mice,and an acetone production at least twice the nitrite release. These authors suggested that multiple forms of cytochrome P-450 are involved, and claimed that nitrite is sequestered in the reaction mixture and that denitrification of 2-NP may involve a reductive or at least non-oxidative pathway as well as an oxidative pathway. They also noted large differences in the rates of hepatic microsomal enzymatic nitrite release among the five strains of mice tested. ...Hepatic microsomes from uninduced rabbits could denitrify a compound related to 2-NP, 2-nitro-1-phenylpropane. In addition to oxidative denitrification, a reductive pathway has been shown to occur in cultured hepatocytes from Wistar rats and in V79 Chinese hamster cells. Nitroreduction was indicated by the fact that the cells formed acetone oxime, the tautomeric form of nitrosopropane.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3；已确认对动物有致癌性，但对人类的相关性未知。
A3; Confirmed animal carcinogen with unknown relevance to humans.
Evaluation: There is inadequate evidence for the carcinogenicity of 2-nitropropane in humans. There is sufficient evidence in experimental animals for the carcinogenicity of 2-nitropropane. Overall evaluation: 2-Nitropropane is possibly carcinogenic to humans (Group 2B).
Following absorption by the gastro-intestinal tract and the lungs, part is eliminated unchanged in the expired air, part excreted in the urine as nitrite and nitrate. There is no evidence of absorption by the skin sufficient to cause systemic injury.
The pharmacokinetics of [14C]-2-nitropropane (2-NP) were studied in male rats exposed for 6 hr to 20 or 154 ppm. At least 40% of the inhaled compound was absorbed. Blood concentrations of 2-NP measured by gas chromatographic analysis decreased in an apparent first order manner (half life = 48 min). Half lives for the biphasic elimination of radioactivity from blood were two to four times longer, indicating that metabolites have a greater potential to accumulate. The major route of excretion was the expired air. About half of the administered radioactivity was recovered as 14CO2. Numerous differences in kinetic parameters observed at the two exposure concentrations indicated nonlinear kinetics at 154 ppm and higher.There were no differences in uptake or exhalation processes between males and females, but metabolic processes differed. A first-order, low-affinity but high capacity metabolic pathway was more than twice as active in females. The saturable pathway was predominant in females at exposure concentrations up to 180 ppm but only up to 60 ppm in males. Because males are more sensitive to hepatoxicity, genotoxicity, and carcinogenicity produced by inhalation of 2-NP, /it was/ concluded that these effects are produced by the metabolite resulting from the first-order pathway.
...Immediately following exposure to 728 mg/cu m (200 ppm) for 3 hr, plasma contained approximately 0.4% as 2-nitropropane (2-NP) and 7.2% as metabolitesof the 2-NP inhaled. The metabolites were mainly acetone but also included a small amount of isopropanol. These percentages were estimated from the results ... and normative data for the laboratory rat, and support rapid pulmonary uptake of 2-NP since 2-NP and its metabolites sequestered elsewhere in the body and loss of metabolized 2-NP during exposure were not considered.
The rate of 2-nitropropane (2-NP) uptake by rats from intraperitoneal injection was examined. Ten minutes after an injection of 25 mg/kg, the blood plasma contained 3.3% of the dose as 2-NP and 1.9% as metabolites, acetone, and isopropanol, indicating an uptake of >5.2% since presumably some of the dose was already lost from the body and to other tissues in the body during this initial period. These percentages were estimated from the data ... and normative data for the laboratory rat. A dose of 50 mg/kg yielded partially dissimilar results. The 10-min average value was low and also had a very large standard deviation. This may have reflected large differences among the rats in their initial uptake rates for 2-NP or an experimental problem such as injection into the gastrointestinal tract rather than the peritoneal cavity. Blood plasma contained, 10 min after injection, only 1.4% of the dose as 2-NP and 1.3% as acetone and isopropanol. These data indicate that uptake from the peritoneal cavity is fairly rapid, and suggest that the relatively slower uptake of the 50-mg/kg dose may have reflected saturation of the uptake mechanisms, since initial concentrations in the plasma did not exceed those following the 25-mg/kg dose.
Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications
作者：Lixing Zhao、Chenyang Hu、Xuefeng Cong、Gongda Deng、Liu Leo Liu、Meiming Luo、Xiaoming Zeng
DOI：10.1021/jacs.0c12318
日期：2021.1.27
Transition metal catalysis that utilizes N-heterocycliccarbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for
A compound represented by the general formula (1):
Q
1
-Q
2
-T
0
-N(R
1
)-Q
3
-N(R
2
)-T
1
-Q
4
(1)
wherein R
1
and R
2
are hydrogen atoms or the like; Q
1
is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q
2
is a single bond or the like; Q
3
is a group
in which Q
5
is an alkylene group having 1 to 8 carbon atoms, or the like; and T
0
and T
1
are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof.
The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
(ALPHA-SUBSTITUTED ARALKYLAMINO AND HETEROARYLALKYLAMINO) PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES, PHARMACEUTICAL COMPOSITIONS THEREOF, AND THEIR USE IN TREATING PROLIFERATIVE DISEASES
申请人：Brown S. David
公开号：US20120252802A1
公开（公告）日：2012-10-04
Provided herein are (alpha-substituted aralkylamino or heteroarylalkylamino) pyrimidinyl and 1,3,5-triazinyl benzimidazoles, e.g., a compound of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for treating proliferative diseases.
Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles from α-Alkenyl-α,β-Enones Derived from Morita-Baylis-Hillman Adducts
作者：Sung Hwan Kim、Jin Woo Lim、Jin Yu、Jae Nyoung Kim
DOI：10.5012/bkcs.2013.34.10.2915
日期：2013.10.20
Convenient synthetic method for 4-arylethylpyrazoles and 4-styrylpyrazoles was developed using $\alpha}$-alkenyl-$\alpha},\beta}$-enones readily accessed from the Morita-Baylis-Hillman reaction. For the synthesis of 4-arylethylpyrazole, the reactions with arylhydrazines needed to be carried out in o-dichlorobenzene under $N_2$ balloon atmosphere. On the other hand, 4-styrylpyrazoles required the reactions in ethanol under $O_2$ balloon atmosphere.
