Quantitative structure-activity relationships of H1-antihistaminic benzimidazole derivatives.
The quantitative structure-activity relationships (QSAR) of 2-(4-substituted-1-piperazinyl)benzimidazole derivatives for antihistaminic activity were examined. Taking into consideration the specific conformations of some derivatives, a significant correlation was obtained using Verloop's STERIMOL parameters B3 and L of the substituent at the 1-position of the benzimidazole nucleus. The results indicated that the derivatives having a substituent with a small breadth and an appropriate length at the 1-position showed potent activity. From the results, a model of the binding site is proposed. The QSAR of side effects (anticholinergic activity and central nervous system depressive effect) were also examined and the results showed that a sterically small substituent at the 1-position was required to decrease side effects.
Iemura
R
R
Ohtaka
H
H
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002492:Central Nervous System Depressants; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D002492:Central Nervous System Depressants; D006634:Histamine H1 Antagonists