Levin, Itai, Fortunato, Mike, Tan, Kian and Coley, Connor (2023) Computer-aided evaluation and exploration of chemical spaces constrained by reaction pathways. AIChE journal.

Abstract

The processes of molecular design and synthetic route selection are necessarily
intertwined during discovery. Computational tools have been developed to facilitate
synthesis planning, but in a discovery setting, finding a single route to a
single molecule of interest may be less important than finding a route that enables
rapid access to a library of analogs. Here, we demonstrate how we can estimate
diversifiability and use it as a criterion during route selection. We illustrate how
the chemical space of synthetically-accessible analogs is influenced by properties
of alternative starting materials or constraints on their cost. Finally, we integrate
these analyses with a synthesizability-constrained hit expansion workflow
in a virtual screening pipeline for focused library expansion around putative hits
to support molecular optimization. As medicinal chemistry and adjacent fields
shift towards more autonomous design and synthesis of new molecules, it will be
increasingly important to embed considerations of synthesizability into molecular
design to ensure that computational recommendations are actionable.

Item Type:	Article
Date Deposited:	31 Oct 2023 00:45
Last Modified:	31 Oct 2023 00:45
URI:	https://oak.novartis.com/id/eprint/50627