Merging nucleophilic phosphine catalysis and photocatalysis for the rapid assembly of 2-oxabicyclo-[2.1.1]hexane scaffolds from feedstock allyl alcohols.

The previously unreported combination of nucleophilic phosphine catalysis and energy transfer catalysis allows for the rapid construction of structurally distinct 2-oxabicyclo[2.1.1]hexanes (2-oxa-BCH) from readily available building blocks with high atom economy.

Access to 2-Oxabicyclo[2.1.1]hexanes and their use in Scaffold Hopping.

Saturated isosteres of the -substituted benzene ring remain rare due to the paucity of methods to access complex bridged systems. Using blue-light-mediated [2 + 2] photocycloaddition chemistry, we have developed a quick and practical route to provide novel 2-oxabicyclo[2.1.

Optimization of a series of novel, potent and selective Macrocyclic SYK inhibitors.

Spleen tyrosine kinase (SYK) is a non-receptor cytoplasmic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signalling, inhibition of SYK has been a target of interest in a variety of diseases. Herein, we report the use of structure-based drug design to discover a series of potent macrocyclic inhibitors of SYK, with excellent kinome selectivity and in vitro metabolic stability.

Virtual Screening in the Cloud Identifies Potent and Selective ROS1 Kinase Inhibitors.

ROS1 rearrangements account for 1-2% of non-small cell lung cancer patients, yet there are no specifically designed, selective ROS1 therapies in the clinic. Previous knowledge of potent ROS1 inhibitors with selectivity over TrkA, a selected antitarget, enabled virtual screening as a hit finding approach in this project. The ligand-based virtual screening was focused on identifying molecules with a similar 3D shape and pharmacophore to the known actives.