Bespoke library docking for 5-HT_2A receptor agonists with antidepressant activity.

ABSTRACT: There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally^1-4. Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investigate structure-based docking of a bespoke virtual library of tetrahydropyridines-a scaffold that is poorly sampled by a general billion-molecule virtual library but is well suited to many aminergic G-protein-coupled receptors. Using three inputs, each with diverse available derivatives, a one pot C-H alkenylation, electrocyclization and reduction provides the tetrahydropyridine core with up to six sites of derivatization^5-7. Docking a virtual library of 75 million tetrahydropyridines against a model of the serotonin

SUBMITTER: Kaplan AL 

PROVIDER: S-EPMC9996387 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature