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Electrochemical Synthesis of the In Human S-oxide Metabolites of Phenothiazine-Containing Antipsychotic Medications
- Source :
- Molecules, Vol 29, Iss 13, p 3038 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
Abstract
- The tractable preparation of Phase I drug metabolites is a critical step to understand the first-pass behaviour of novel chemical entities (NCEs) in drug discovery. In this study, we have developed a structure–electroactivity relationship (SeAR)-informed electrochemical reaction of the parent 2-chlorophenothiazine and the antipsychotic medication, chlorpromazine. With the ability to dial-in under current controlled conditions, the formation of S-oxide and novel S,S-dioxide metabolites has been achieved for the first time on a multi-milligram scale using a direct batch electrode platform. A potential rationale for the electrochemical formation of these metabolites in situ is proposed using molecular docking to a cytochrome P450 enzyme.
- Subjects :
- electrochemistry
metabolite
phenothiazine
chlorpromazine
Organic chemistry
QD241-441
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 29
- Issue :
- 13
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.88b96f4184854f24b06da0165f0b0495
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules29133038