Do Drug-likeness Rules Apply for Oral Prodrugs?

Do Drug-likeness Rules Apply for Oral Prodrugs? ChemMedChem. 2021 Jan 20;: Authors: Protti ÍF, Rodrigues DR, Fonseca SK, Alves RJ, de Oliveira RB, Maltarollo VG Abstract This paper describes a comparative analysis of the physicochemical and structural properties between prodrugs and their corresponding drugs regarding drug-likeness rules. The dataset used in this work was obtained from the DrugBank. Sixty-five pairs of prodrugs/drugs were retrieved and divided into the following categories: carrier-linked to increase hydrophilic character, carrier-linked to increase absorption, and bioprecursors. We compared physicochemical properties related to drug-likeness between prodrugs and drugs. Our results show that prodrugs do not always follow Lipinski's Rule of 5, especially since we observed 15 prodrugs with more than 10 hydrogen bond acceptors and 18 ones with molecular weight greater than 500 Da. This fact highlights the importance of extending Lipinski's rules to encompass other parameters since both strategies (filtering of drug-like chemical libraries and prodrugs design) aim to improve the bioavailability of compounds. Therefore, a critical reasoning is fundamental to determine whether a structure has drug-like properties or could be considered a potential orally active compound in the drug design pipeline. PMID: 33471444 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research