Piportil, Rhone-Poulenc Rorer
Pipotiazine is drug repurposing for Covid-19: discovery of potential small-molecule inhibitors of spike protein-ACE2 receptor interaction through virtual screening and consensus scoring.
10-(3-Tetrahydropyranyloxypropyl)phenthiazine-2-sulfonic acid dimethylamide prepared by condensing 1-chloro-3-tetrahydropyranyloxy propane with phenthiazine-2-sulfonic acid dimethylamide (melting point 140°C) in xylene in the presence of sodamide.
10-(3-Hydroxypropyl)phenthiazine-2-sulfonic acid dimethylamide was prepared by the action of hydrochloric acid in ethanol on 10-(3tetrahydropyranyloxypropyl)phenthiazine-2-sulfonic acid dimethylamide.
10-(3-Methanesulphonyloxypropyl)phenthiazine-2-sulphonic acid dimethylamide, was obtained by condensing methanesulphonyl chloride in anhydrous pyridine with 10-(3-hydroxypropyl)phenthiazine-2-sulfonic acid dimethylamide.
10-(3-Methanesulphonyloxypropyl)phenthiazine-2-sulfonic acid dimethylamide and 4-hydroxyethyl piperidine in toluene were heated under reflux with stirring. The reaction mixture was allowed to cool and water was added. The resulting toluene solution layer was decanted and washed twice with water. The toluene solution was then stirred with 5% hydrochloric acid. The hydrochloride of the desired phenthiazine base precipitated in gummy condition in the aqueous layer. This was decanted and treated with sodium hydroxide. It was then extracted three times with ethyl acetate. The extracts were dried over sodium sulfate, filtered and concentrated in vacuum. A resinous product was obtained. This product was dissolved in a mixture of benzene and cyclohexane and chromatographed on a column containing alumina. The chromatographed product was eluted successively with mixtures of benzene and cyclohexane and then with benzene and finally with a mixture of benzene and ethyl acetate. The eluates were evaporated to yield a crude product. This product was recrystallised from aqueous ethanol and yielded 10[3-[4-(2-hydroxyethyl)piperidyl]propyl]phenthiazine-2-sulfonic acid dimethylamide.
