Structure-activity relationships of benzimidazole carbamates as inhibitors of mammalian tubulin, in vitro.
The structure-activity relationships of thirty-two methyl (5(6)-substituted benzimidazol-2yl) carbamates as inhibitors of the rate of polymerisation of mammalian tubulin have been investigated. The size or some colinear physico-chemical characteristic of the substituent in the 5 (or 6)-position has a profound effect on potency. The presence of branching with or without a commensurate increase in the polarity of the 5(6)-substituent adjacent to the benzimidazole ring (alpha-position) resulted in a loss of activity. The nature of the overall site, as reflected by the quantitative models, could relate to either the hydrophobicity or molar volume of the 5 (or 6)-substituents.
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008954:Models, Biological; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators
D000871:Anthelmintics; D000935:Antifungal Agents; D001562:Benzimidazoles; D050257:Tubulin Modulators