Synthesis and Biological Evaluation of Novel 2-(Piperidin-4-yl)-1,2,3,4-tetrahydroisoquinoline and 2-(Piperidin-4-yl)decahydroisoquinoline Antimycotics

Abstract

Piperidine antimycotics like fenpropidin are well established in agrochemistry. On the other hand, numerous isoquinoline derivatives show remarkable antimycotic effects. Here we present a series of 13 hybrid molecules of both lead structures, which were prepared using reductive amination as key reaction step. Pre-screening against Yarrowia lipolytica resulted in a batch of promising candidates whose antifungal efficacy was further evaluated against clinically relevant species. In these assays, complete growth inhibition was seen for five or six compounds against C. albicans or C. krusei, respectively, and in two against C. glabrata, whereas no antifungal activity was observed against mold isolates, with the exception of 6i, which led to complete growth inhibition of aspergilli, and two compounds (6k and 6 l) that were able to inhibit Rhizopus arrhizus.