Tag: 489.3942

Metabolism of ketoconazole and deacetylated ketoconazole by rat hepatic microsomes and flavin-containing monooxygenases was written by Rodriguez, Rosita J.;Acosta, Daniel Jr.. And the article was included in Drug Metabolism and Disposition in 1997.Product Details of 67914-61-8 This article mentions the following:

Ketoconazole (KT) has been reported to cause hepatotoxicity, which is probably not mediated through an immunoallergic mechanism. Although KT is extensively metabolized by hepatic microsomal enzymes, the nature, route of formation, and toxicity suspected metabolites are largely unknown. Recent reports indicate that N-deacetyl ketoconazole (DAK) is a major initial metabolite in mice, which, like lipophilic-4-alkylpiperazines, is susceptible to successive oxidative attacks on the N-1 position producing ring-opened dialdehydes. The rate of formation of DAK from hepatic rat microsomal incubations of KT was determined by HPLC. The rate of disappearance for KT was almost equal to the rate of DAK formation: 5.96 and 5.88 μM/h, resp. Also, the potential bioactivation of DAK was evaluation by measuring substrate activity of DAK with purified pig liver flavin-containing monooxygenase (FMO) and rat liver microsomes. Activity was measured by following DAK-dependent oxygen uptake polarog. at 37°C in pyrophosphate buffer (pH 8.8) containing the glucose-6-phosphate NADPH-generating system. The K_M‘s of DAK were 34.6 and 77.4 μM for the purified FMO and rat microsomal FMO, resp. Lastly, DAK was found to be metabolized by an NADPH-dependent rat liver microsomal monooxygenases at pH 8.8 to two metabolites as determined by HPLC. Heat inactivation of rat liver microsomal FMO abolished the formation of these metabolites from DAK. SKF-525A and anti-rat NADPH cytochrome P 450 reductase did not inhibit this reaction. These results suggest that deacetylation of KT yields a major product, DAK, for further metabolism by microsomal monooxygenases that seem to be FMO-related. In the experiment, the researchers used many compounds, for example, rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8Product Details of 67914-61-8).

rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Product Details of 67914-61-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Synthesis of ketoconazole derivatives was written by Ryu, Jae Chun;Lee, Kwang Jae;Lee, Sang Hee. And the article was included in Bulletin of the Korean Chemical Society in 2003.Product Details of 67914-61-8 This article mentions the following:

For the drug master file (DMF) of ketoconazole, four impurities contained in ketoconazole were synthesized. During the synthesis of I, a new synthetic method of 1,4-dihydropyrazine was established. To oxidize the aminoalc. of I to the aminal I, the standard Swern oxidation condition was modified to mask the nucleophilicity of the amino group temporarily using one equivalent of acetic acid. Derivative II was synthesized via regioselective bromination at the I position of the 4-aminophenol derivative of II using Br₂ in the presence of p-TsOH. The etherification of aryl bromide with a phenol derivative compound was accomplished by a modification of the general Cu-mediated reaction condition using excess of the phenol derivative itself as a solvent at elevated temperature (190 °C). In the experiment, the researchers used many compounds, for example, rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8Product Details of 67914-61-8).

rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Product Details of 67914-61-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Assessment of community-wide antimicrobials usage in Eastern China using wastewater-based epidemiology was written by Xu, Like;Zang, Jinxin;Cong, Wenjuan;Holton, Elizabeth;Jiang, Lufang;Sheppard, Samuel K.;Wang, Yingying;Wang, Na;Weeks, Jason;Fu, Chaowei;Jiang, Qingwu;Lambert, Helen;Kasprzyk-Hordern, Barbara. And the article was included in Water Research in 2022.Recommanded Product: 67914-61-8 This article mentions the following:

Wastewater-based epidemiol. (WBE) has potential to identify the epidemiol. links between people, animals, and the environment, as part of antimicrobial resistance (AMR) surveillance. In this study, we investigated six wastewater treatment plants (WWTPs) serving six communities located in two regions in Eastern China: Site A in Zhejiang and site B in Jiangsu province to assess the public use of antimicrobial agents (AA). Fifty antimicrobials and 24 of their metabolites were quantified using ultraperformance liquid chromatog. coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS). Spatiotemporal trends were established for measured concentrations daily loads, and population-normalized daily loads. Daily AA mass loads varied between 1.6 g/day and 324.6 g/day reflecting the WWTP scales, with macrolides and β-lactams showing the highest overall environmental burden at 223.7 g/day and 173.7 g/day, resp. Emissions of antibiotic residues from manufacturing have been observed with the peak daily load 12-fold higher than the overall load from a community serving a population of over 600,000. Community exposure levels of 225.2 ± 156.2 mg/day/1000 inhabitant and 351.9 ± 133.5 mg/day/1000 inhabitant were recorded in site A and B, resp. Paired parent-metabolites anal. identified a large proportion (64-78%) of un-metabolised metronidazole and clindamycin at site B, indicating improper disposal of unused drugs either in the community or in livestock production Consumption levels, calculated via WBE, suggested relatively low antimicrobial usage in Eastern China compared to other areas in China. This first application of WBE in Eastern China to assess the community-wide exposure to AAs has potential to inform regional antimicrobial stewardship. In the experiment, the researchers used many compounds, for example, rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8Recommanded Product: 67914-61-8).

rel-1-(4-(((2R,4S)-2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine (cas: 67914-61-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Recommanded Product: 67914-61-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics