176485-92-0Relevant academic research and scientific papers
Synthesis, absolute configuration, and biological profile of the enantiomers of trans-[2-(2,6-dimethoxyphenoxy)ethyl][(3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2- yl)methyl]amine (mephendioxan), a potent competitive α1A-adrenoreceptor antagonist
Quaglia, Wilma,Pigini, Maria,Tayebati, Seyed K.,Piergentili, Alessandro,Giannella, Mario,Leonardi, Amedeo,Taddei, Carlo,Melchiorre, Carlo
, p. 2253 - 2258 (1996)
The enantiomers of trans-[2-(2,6-dimethoxyphenoxy)ethyl][(3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2- yl)methyl]amine (mephendioxan, 2) were synthesized from the chiral trans-3-p-tolyl- 2,3-dihydro-1,4-benzodioxin-2-carboxylic acids [(+)-3 and (-)-3] which in turn were obtained through the resolution of the racemic acid with (R)- and (S)-α-methylbenzylamine. Comparison of CD spectra of the enantiomers of 2 with that of (2S,3S)-3-methyl-2-phenyl-1,4-benzodioxane allowed the assignment of the 2S,3S configuration to the (-)-enantiomer of 2 and of the 2R,3R configuration to the other enantiomer. The binding profile of the enantiomers of 2 was assessed at α1, α2, D2, and 5-HT1A receptors, in comparison to WB 4101 (1), 5-methylurapidil, and (+)- niguldipine. In addition, the two enantiomers were investigated at native and cloned α1-adrenoreceptor subtypes. (-)-2 was 10-30 times as potent as the (+)-enantiomer at α1- adrenoreceptor subtypes in both functional and binding assays. It was 36-fold selective for the α1A- versus α1B-adrenoreceptor and 60- and 20-fold selective in binding to the α1a- adrenoreceptor relative to α1b and α1d subtypes, respectively. Furthermore, the enantiomer (-)-2 displayed selectivities of 12000-, 2500-, and 250-fold in binding to α1a-adrenoreceptors relative to α2-adrenoreceptors and 5-HT1A and D2 receptors. These results indicate that (-)-2 may be a valuable tool in the characterization of α1-adrenoreceptor subtypes.
