[Comparative molecular field analysis(CoMFA) of allylamine and benzylamine antimycotics].
"Active analog approach" has been employed to search the pharmacophoric conformation of the allylamine and benzylamine antimycotics. A local minimum energy conformation, which is very similar to the crystallographically determined coordinate of naftifine or terbinafine, has been applied to build all compounds. Comparative molecular field analysis (CoMFA) has been used to examine the correlations between the activities against 6 common human pathogenic fungi and the physicochemical properties of 62 allylamine and benzylamine compounds which had been aligned by rms fit rule. The predictive abilities of the resulting 3D-QSAR models have been tested by 8 new synthetic compounds and 5 reported compounds. Finally, we propose an interaction pattern between allylamine, benzylamine antimycotics and the active site of pseudoreceptor based on the results of 2D-QSAR and 3D-QSAR.
Ji
H
H
School of Pharmacy, Second Military Medical University, Shanghai 200433.
Zhang
W
W
Zhou
Y
Y
Lu
J
J
Zhu
J
J
Li
K
K
Chen
W
W
Liu
N
N
D000499:Allylamine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects; D008864:Microsporum / Q000187:drug effects; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D014249:Trichophyton / Q000187:drug effects
D000935:Antifungal Agents; D001596:Benzylamines; D000499:Allylamine