115931-01-6Relevant articles and documents
Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms
Renwick,Mistry,Ball,Walters,Kao,Lake
, p. 337 - 348 (1998)
1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in human liver microsomal preparations and in cDNA-expressed human cytochrome P450 (CYP) isoforms. 2. Human liver microsomes catalysed the NADPH-dependent N-deethylation of ZAL to DZAL (CL-284,859), but not to two other known in vivo metabolites, namely M1 (CL-345,644) and M2 (CL-345,905). Sigmoidal kinetic plots were observed for ZAL deethylation indicating positive cooperativity. 3. The metabolism of ZAL to DZAL was determined in a characterized bank of 24 human liver microsomal preparations. Good correlations (r2 = 0.734-0.937) were observed with caffeine 8-hydroxylase, diazepam 3-hydroxylase, dextromethorphan N-demethylase and testosterone 2β- , 6β- and 15β-hydroxylase activities, which are all catalysed by CYP3A isoforms. In contrast, poor correlations (r2 = 0.152-0.428) were observed for enzymatic markers for CYP1A2, CYP2A6, CYP2C9/10, CYP2D6, CYP2E1 and CYP4A9/11. 4. The metabolism of ZAL to DZAL in human liver microsomes was inhibited to 6-15 % of control by 5-50 μM of the mechanism-based CYP3A inhibitor troleandomycin. Whereas some inhibition of DZAL formation was observed in the presence of 200 μM diethyldithiocarbamate, 5-50 μM furafylline, 2-20 μM sulphaphenazole, 50-500 μM S-mephenytoin and 1-10 μM quinidine had little effect. 5. Using human B-lymphoblastoid cell microsomes containing cDNA-expressed CYP isoforms, ZAL was metabolized to DZAL by CYP3A4, but not to any great extent by CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. 6. In contrast with ZAL, the NADPH- dependent N-deethylation of M2 to M1 proceeded at only a very low rate with both human liver microsomes and cDNA-expressed CYP3A4. 7. In summary, by correlation analysis, chemical inhibition studies and the use of cDNA- expressed CYPs, ZAL N-deethylation to DZAL in human liver appears to be catalysed by CYP3A isoforms.
Preparation method of indinplon intermediate
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Paragraph 0024-0027, (2021/06/12)
The invention discloses a preparation method of an indanplon intermediate, and belongs to the technical field of medicinal chemistry. According to the invention, simple and cheap m-nitrobenzaldehyde and triethylamine are adopted as raw materials, and a core skeleton of the indeneplon is efficiently and highly selectively constructed through a one-pot cascade reaction without transition metal catalysis, so that generation of isomers is avoided, generation of byproducts is reduced, the yield of a target product is improved, and the synthesis cost is reduced; and subsequently, simple nitro reduction modification is carried out to prepare the indinplon intermediate. In addition, the reaction condition for preparing the indianplon intermediate is mild, operation is simple and convenient, and the method is suitable for industrial production.
IMMUNODETECTION AND QUANTIFICATION OF PYRAZOLOPYRIMIDINE SEDATIVES
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, (2011/02/24)
The invention relates to novel immunogens, antibodies, methods and kits for use in immunoassays to detect and quantify zaleplon, metabolites of zaleplon and indiplon. These are the first described immunoassays for these compounds and have greater sensitivity than alternative analytical techniques.
