Comparison of metabolic pathways of different α-N-heterocyclic thiosemicarbazones.

ABSTRACT: Clinical failure of novel drugs is often related to their rapid metabolism and excretion. This highlights the importance of elucidation of their pharmacokinetic profile already at the preclinical stage of drug development. Triapine, the most prominent representative of α-N-heterocyclic thiosemicarbazones, was investigated in more than 30 clinical phase I/II trials, but the results against solid tumors were disappointing. Recent investigations from our group suggested that this is, at least partially, based on the fast metabolism and excretion. In order to establish more detailed structure/activity/metabolism relationships, herein a panel of 10 different Triapine derivatives was investigated for their metabolic pathways. From the biological point of view, the panel consists of terminally di

SUBMITTER: Pelivan K 

PROVIDER: S-EPMC5849672 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature