The influence of calculated physicochemical properties of compounds on their ADMET profiles.

The influence of calculated physicochemical properties of compounds on their ADMET profiles.
Bioorg Med Chem Lett. 2021 Jan 25;:127825
Authors: Ma S, McGann M, Enyedy IJ
Abstract
We analyzed the influence of calculated physicochemical properties of more than 20,000 compounds on their P-gp and BCRP mediated efflux, microsomal stability, hERG inhibition, and plasma protein binding. Our goal was to provide guidance for designing compounds with desired pharmacokinetic profiles. Our analysis showed that compounds with ClogP less than 3 and molecular weight less than 400 will have high microsomal stability and low plasma protein binding. Compounds with logD less than 2.2 and/or basic pKa larger than 5.3 are likely to be BCRP substrates and compounds with basic pKa less than 5.2 and/or acidic pKa less than 13.4 are less likely to inhibit hERG. Based on these results, compounds with MW < 400, ClogP < 3, basic pKa < 5.2 and acidic pKa < 13.4 are likely to have good bioavailability and low hERG inhibition.
PMID: 33508464 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - January 25, 2021 Category: Chemistry Authors: Ma S, McGann M, Enyedy IJ Tags: Bioorg Med Chem Lett Source Type: research