EnglishQuantitative structure-activity relationship analysis using theoretical molecular descriptors was done on a set of 30 1,4-benzodioxan (WB-4101) related compounds which are alpha1-adrenoceptor antagonists. The results obtained confirm quantitatively and in terms of reactivity and molecular shape descriptors, the results of previous qualitative structure-activity relationship studies. It was found that the protonated amine function plays a crucial role in the potency of the alpha1-adrenoceptor antagonism due to a charge reinforced hydrogen bond with a primary nucleophilic site of the receptor. Furthermore, the more electrophilic (high SN1LUMO values) the NH2+ group, the stronger the charge reinforced hydrogen bond with the receptor and the higher the blocking activity. It was also found that the three-dimensional shape of the antagonists is more similar to the shape of the most active reference molecule (WB-4101) the more potent antagonists are. Finally, the reactivity (E(LUMO)) and the ad hoc shape (V(D)(norm)) descriptors were used to obtain a bilinear equation which accounts for about 77% of the total variance in the pharmacological data.
| Data di pubblicazione: | 1992 |
| Titolo: | Molecular modeling and quantitaive structure activity relationship analysis using theoretical descriptors of 1,4-benzodioxan (WB-4101) related-compounds alpha-1-adrenergic antagonists |
| Autore/i: | P., Venturelli; Menziani, Maria Cristina; Cocchi, Marina; Fanelli, Francesca; DE BENEDETTI, Pier Giuseppe |
| Autore/i UNIMORE: | |
| Rivista: | |
| Volume: | 95 |
| Pagina iniziale: | 327 |
| Pagina finale: | 340 |
| Codice identificativo ISI: | WOS:A1992KH24100023 |
| Codice identificativo Scopus: | 2-s2.0-0005185079 |
| Citazione: | Molecular modeling and quantitaive structure activity relationship analysis using theoretical descriptors of 1,4-benzodioxan (WB-4101) related-compounds alpha-1-adrenergic antagonists / P., Venturelli; Menziani, Maria Cristina; Cocchi, Marina; Fanelli, Francesca; DE BENEDETTI, Pier Giuseppe. - In: JOURNAL OF MOLECULAR STRUCTURE. THEOCHEM. - ISSN 0166-1280. - STAMPA. - 95(1992), pp. 327-340. |
| Tipologia | Articolo su rivista |
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