Estudio teórico de dimaprit y homólogos

ENRIZ R D; M.R.ESTRADA; G.M.CIUFFO; E.A.JAUREGUI

Journal of the Argentine Chemical Society

ASOCIACIÓN QUÍMICA ARGENTINA

Lugar: Buenos Aires; Año: 1990 vol. 78 p. 221 - 235

0365-0375

A conformational study on dimaprirt,, (a highly selectiveH¡-histanwne receptor agonist, and two o f its weak/wra.ctive homologues(nordimapriit and SK&F 92054) w,u; carried (aut using MNDOcalculatiows. A full optimization of the ueometriod.11parameters, on thedifferent oonfigurational isomers, was mrried Ollt.Severa/ low-energy conformations ~ obtailffli. ff{J)lr rilimaprit, some ofwhich we,re similar to those previom.fy obtained ~ using molecularmechanics calculations. For norrlim11Prit, the glolH,Jl mínimum was anextreme/y folded confo;rmation. Due tJc, the smalkr üze of nordimaprit.its conformation did .not present disttances between po,tentiat:y activegroups similar to those of dimaprit. Also the e/ectror.1ic distributionobtained /i@r this molecule was different to that obseroed in dimaprit.For SK&F !92054, the stteric hindrance of the methyl sub·stituent in theisothiourec ,group conslll«lins the rotational possibilities 1?( this group.Many reasons may be mesponsible for the low activity of dimaprithomologues, but the present results suggest that the lou·J activity ofdimaprit ho11JZologues is llJ consequence of the different spatial distributionof active groups ~sented by their low-energy conformations.