BIreactive: Expanding the Scope of Reactivity Predictions to Propynamides.

ABSTRACT: We present the first comprehensive study on the prediction of reactivity for propynamides. Covalent inhibitors like propynamides often show improved potency, selectivity, and unique pharmacologic properties compared to their non-covalent counterparts. In order to achieve this, it is essential to tune the reactivity of the warhead. This study shows how three different in silico methods can predict the in vitro properties of propynamides, a covalent warhead class integrated into approved drugs on the market. Whereas the electrophilicity index is only applicable to individual subclasses of substitutions, adduct formation and transition state energies have a good predictability for the in vitro reactivity with glutathione (GSH). In summary, the reported methods are well suited to estimate the

SUBMITTER: Hermann MR 

PROVIDER: S-EPMC9866037 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature