Synthesis and biological evaluation of novel N-alkyl tetra- and decahydroisoquinolines: novel antifungals that target ergosterol biosynthesis.

A series of N-alkyl trans-decahydroisoquinoline, 1,2,3,4-tetrahydroisoquinoline, and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized starting from the respective secondary amines by N-alkylation with alkyl bromides. The compounds with C11-alkyl chains showed antifungal potency comparable to clotrimazole, and inhibit enzymes of the ergosterol biosynthesis (Δ14-reductase and Δ8,7-isomerase), depending on the heterocyclic scaffold and the investigated species.