123323-99-9Relevant articles and documents
4-ARYL-3-(DIMETHYLAMINOMETHYL)THIACYCLOHEXAN-4-OLS INCLUDING THE THIA ANALOGUE OF TRAMADOL; SYNTHESIS AND ANALGETIC ACTIVITY
Urban, Jiri,Svatek, Emil,Ryska, Miroslav,Metys, Jan,Wildt, Stanislav,Protiva, Miroslav
, p. 1340 - 1351 (2007/10/02)
Mannich reaction of thiacyclohexan-4-one with dimethylamine and paraformaldehyde afforded 3-(dimethylaminomethyl)thiacyclohexan-4-one (XIV) which was subjected to reactions with a series of arylmagnesium bromides.The products were mixtures of trans- and cis-amino alcohols III-XII from which the predominating trans-components were mostly obtained by crystallization of hydrochlorides or chromatography of bases.The tramadol (I) analogue, i.e. the 3-methoxy compound V, was prepared in the form of both racemates and their relative configuration was confirmed by the IR spectra.Compound V was demethylated to the 3-hydroxyphenyl analogue XIII, transformed to the bis-onium salt XVI, partially N-demethylated to the N-monodemethyl analogue XVII, and oxidized to the sulfoxide XX and to the sulfone N-oxide XXI.Some of the amino alcohols (III-V, VIII, IX, XIII) showed clear analgetic activity in the writhing syndrome inhibition test in mice; the 3-methoxy and 3-hydroxy compounds (V and XIII) were the most active ones, the latter being slightly more active than tramadol (I).
