N,N,beta-trimethyl-10H-phenothiazine-10-propylamine 5,5-dioxide monohydrochloride Chemical Properties

InChI

InChI=1S/C18H22N2O2S.ClH/c1-14(12-19(2)3)13-20-15-8-4-6-10-17(15)23(21,22)18-11-7-5-9-16(18)20;/h4-11,14H,12-13H2,1-3H3;1H

InChIKey

NPMMOYKGIWLASW-UHFFFAOYSA-N

SMILES

C(N1C2=CC=CC=C2S(=O)(=O)C2C=CC=CC1=2)C(C)CN(C)C.Cl

N,N,beta-trimethyl-10H-phenothiazine-10-propylamine 5,5-dioxide monohydrochloride Usage And Synthesis

Originator

Doxergan,Specia,France,1964

Uses

Oxomemazine hydrochloride is a phenothiazine-based histamine H1-receptor blocker with pronounced antimuscarinic properties. Oxomemazine hydrochloride is a selective antagonist for muscarinic M1 receptor, displays about 20-fold difference in the affinity for high (Ki= 84 nM, M1 receptor) and low (Ki= 1.65 μM, M2 receptor) affinity sites[1]. Oxomemazine hydrochloride an antihistamine and anticholinergic agent used for the study of cough treatment[2].

Manufacturing Process

Phenothiazine is reacted with 3-dimethylamino-2-methylpropyl chloride in the presence of sodium amide to give 3-(10-phenthiazinyl)-2-methyl-1dimethylaminopropane. 11.9 g of of this intermediate is dissolved with agitation in glacial acetic acid (120 cc). Pure sulfuric acid (d = 1.83; 0.5 cc) is added and a mixture of glacial acetic acid (10 cc) and hydrogen peroxide (8.5 cc of a solution containing 38 g of hydrogen peroxide in 100 cc) is then run in over 20 minutes. The temperature rises from 25°C to 35°C and is then kept at 60°C for 18 hours. The mixture is cooled and water (150 cc) is added and, with cooling, aqueous sodium hydroxide (d = 1.33; 220 cc). The resulting mixture is extracted with ethyl acetate (3 x 100 cc), the solvent is evaporated on a water bath and the residue is recrystallized from heptane (150 cc). 3(9,9-dioxy-10-phenthiazinyl)-2-methyl-1-dimethylaminopropane (78 g) is obtained, MP 115°C.
The corresponding hydrochloride prepared in ethyl acetate and recrystallized from a mixture of ethanol and isopropanol melts at 250°C.

Therapeutic Function

Antihistaminic

IC 50

mGluR 1: 84 nM (Ki); mGluR2: 1.65 μM (Ki)

References

[1] S W Lee, et al.Selectivity of oxomemazine for the M1 muscarinic receptors.Arch Pharm Res. 1994 Dec;17(6):443-51. DOI:10.1007/BF02979123
[2] M S Siddegowda, et al.Oxomemazine hydro-chloride. Acta Crystallogr Sect E Struct Rep Online. 2011 Aug 1;67(Pt 8):o1875. DOI:10.1107/S1600536811025372

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