Continuous‐Flow Synthesis of Phenothiazine Antipsychotics: A Feasibility Study

Abstract

The continuous flow synthesis of a model phenothiazine antipsychotic is presented herein, using 3‐chloropropionyl chloride as a central building block. The basic phenothiazine‐derived scaffold is (atom)‐efficiently and mildly synthesized with the aim to present continuous flow technology as a contributor to fast and efficient syntheses of challenging APIs, that are nowadays experiencing supply disruptions and global shortages.

Interpol review of controlled substances 2016–2019

“…Phenothiazines: 2016 LC-MS/MS method for the screening and confirmation of 28 veterinary drug and metabolite residues (nitroimidazoles, benzimidazoles, sulfones, quinolones, macrolides, phenothiazines, pyrethroids and others) [ 1086 ]; heterologous competitive indirect ELISA for the determination of five phenothiazines (chlorpromazine, promethazine and perphenazine, acepromazine and fluphenazine) [ 1087 ]; synthesis and characterization by H-1 NMR, C-13 NMR and ESI-MS [ 1088 ]; UPLC MS/MS method for 210 drugs (including phenothiazines) [ 1089 ]; 2017 simultaneous electroanalytical detection of Chlorpromazine and Thioridazine [ 1090 ]; ELISA method for determination of 5 phenothiazine drugs [ 1091 ]; SPE method for phenothiazines [ 1092 ]; ELISA for the detection of phenothiazines in animal feed [ 1093 ]; LC-MS/MS method for quantification of phenothiazines [ 1094 ]; 2018 SPE UHPLC-DAD method for detection of promethazine (PMZ) and chlorpromazine (CPZ) [ 1095 ]; CE coupled with ultraviolet absorption for the simultaneous separation of chiral phenothiazine drugs at nanomolar concentration levels [ 1096 ]; SPE method for phenothiazines and benzodiazepines [ 1097 ]; imprinted polymer based chemiluminescence array capable of simultaneous determining phenothiazines and benzodiazepines [ 1098 ]; chemiluminescence array sensor for the simultaneous determination of four phenothiazines and five benzodiazepines [ 1099 ]; 2019 continuous flow synthesis of a model phenothiazine antipsychotic [ 1100 ]; review [ 1101 ].…”

The impact of fluphenazine withdrawal: a mirror-image study

“…Fluphenazine decanoate is a first-generation antipsychotic (FGA) agent (most common brand name is Modecate) belonging to the phenothiazine class of antipsychotic medications. Fluphenazine was introduced in 1959 (Matar et al, 2013) and was withdrawn from Ireland and other countries in 2018 due to manufacturing difficulties with the active pharmaceutical ingredient (Movsisyan et al, 2019). Fluphenazine was licenced for use as an antipsychotic medication for patients with psychotic disorders including schizophrenia, schizoaffective disorder, delusional disorder and bipolar affective disorder (Health Products Regulatory Authority 2018; Siragusa et al, 2023).…”