Abstract
The tractable preparation of phase-I drug metabolites is a critical step to understand the first-pass behaviour of novel chemical entities in drug discovery. In this study we have developed a structure electroactivity relationship (SeAR) informed electrochemical reaction of the parent 2-chlorophenothiazine and anti-psychotic, chlorpromazine. 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 multimilligram 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.
Supplementary materials
Title
Supporting Information
Description
General Experimental Methods
General Procedures
Compound Characterization
NMR and MS data
HPLC data
LCMS data
IR data
HPLC-LCMS data 2-Chlorophenothiazine Fractions
Cyclic voltammetry data on analogues
Molecular docking studies
Biotransformer results
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