Mesoridazine

Mesoridazine (Serentil) is a phenothiazine class drug that is used in the treatment of schizophrenia.^[2] It is one of the active metabolites of thioridazine. The drug's name is derived from the methylsulfoxy and piperidine functional groups in its chemical structure.

Mesoridazine

Clinical data
Trade names	Serentil
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a682306
Routes of administration	Oral, intravenous
Drug class	Typical antipsychotic
ATC code	N05AC03 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[1] In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	4%
Metabolism	Hepatic/renal
Elimination half-life	24 to 48 hours
Excretion	Biliary and renal
Identifiers
IUPAC name 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfinylphenothiazine
CAS Number	5588-33-0 Y
PubChem CID	4078
IUPHAR/BPS	7227
DrugBank	DB00933 Y
ChemSpider	3936 Y
UNII	5XE4NWM740
KEGG	D02671 Y
ChEBI	CHEBI:6780 Y
ChEMBL	ChEMBL1088 Y
CompTox Dashboard (EPA)	DTXSID3023265
Chemical and physical data
Formula	C21H26N2OS2
Molar mass	386.57 g·mol−1
3D model (JSmol)	Interactive image
Melting point	130 °C (266 °F)
Solubility in water	insoluble mg/mL (20 °C)
SMILES O=S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C
InChI InChI=1S/C21H26N2OS2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(26(2)24)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3 Y Key:SLVMESMUVMCQIY-UHFFFAOYSA-N Y
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It has central antiadrenergic, antidopaminergic, antiserotonergic and weak muscarinic anticholinergic effects.

Serious side effects include akathisia, tardive dyskinesia and the potentially fatal neuroleptic malignant syndrome.

Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.^[3]

Mesoridazine is on the FDA's Discontinued Drug Product List.^[4]

Synthesis

Thieme Synthesis:^[5][6] Patent:^[7]

2-Methylthiophenothiazine [7643-08-5] (1) is treated with acetic anhydride] to give the protected amide, ie 10-acetyl-2-methylthiophenothiazine, CID:69367526. Oxidation of this by means of hydrogen peroxide and removal of the acetyl protecting group with potassium carbonate in methanol solution gives 2-methylsulfonylphenothiazine [23503-68-6] (3). Introduction of the sidechain by alkylation with 2-(2-chlorethyl)-1-methylpiperidine [50846-01-0] (6) in the presence of sodamide, afforded the desired mesoridazine (5).