AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Oxidative Addition Complexes as Precatalysts for Cross-Coupling Reactions Requiring Extremely Bulky Biarylphosphine Ligands

In this report, we describe the application of palladium-based oxidative addition complexes (OACs) as effective precatalysts for C-N, C-O, and C-F cross-coupling reactions with a variety of (hetero)arenes. These complexes offer a convenient alternative to previously developed classes of precatalysts, particularly in the case of the bulkiest biarylphosphine ligands, for which palladacycle-based precatalysts do not readily form. The precatalysts described herein are easily prepared and stable to long-term storage under air.National Institutes of Health (U.S.) (Award GM46059)National Institutes of Health (U.S.) (Award GM58160

Unexpected Formation of Hexasubstituted Arenes Through a Twofold Palladium-Mediated Ligand Arylation

A rearrangement reaction of biarylphosphine-supported Pd(II) complexes was employed to synthesize 1,3,5-triaryl 2,4,6-triisopropylbenzene compounds, a class of molecules that has not previously been reported. The strain of the central hexasubstituted ring was investigated via X-ray crystallography. <br /

Unexpected Formation of Hexasubstituted Arenes through a 2-fold Palladium-Mediated Ligand Arylation

© 2019 American Chemical Society. A rearrangement reaction of biarylphosphine-supported Pd(II) complexes was employed to synthesize 1,3,5-triaryl 2,4,6-triisopropylbenzene compounds, a class of molecules that has not previously been reported. The strain of the central hexasubstituted ring was investigated via X-ray crystallography

Oxidative Addition Complexes as Precatalysts for Cross-Coupling Reactions Requiring Extremely Bulky Biarylphosphine Ligands

In this report, we describe the application of palladium-based oxidative addition complexes (OACs) as effective precatalysts for C–N, C–O, and C–F cross-coupling reactions with a variety of (hetero)­arenes. These complexes offer a convenient alternative to previously developed classes of precatalysts, particularly in the case of the bulkiest biarylphosphine ligands, for which palladacycle-based precatalysts do not readily form. The precatalysts described herein are easily prepared and stable to long-term storage under air

Oxidative Addition Complexes as Precatalysts for Cross-Coupling Reactions Requiring Extremely Bulky Biarylphosphine Ligands

In this report, we describe the application of palladium-based oxidative addition complexes (OACs) as effective precatalysts for C–N, C–O, and C–F cross-coupling reactions with a variety of (hetero)­arenes. These complexes offer a convenient alternative to previously developed classes of precatalysts, particularly in the case of the bulkiest biarylphosphine ligands, for which palladacycle-based precatalysts do not readily form. The precatalysts described herein are easily prepared and stable to long-term storage under air