Joseph Therrien

TL;DR: This medicinal chemistry effort culminated in the identification of 52, a potent and highly selective inhibitor of PI3Kδ that demonstrates efficacy in a rat model of arthritis.

TL;DR: A fluoroquinolone prodrug was prepared and shown to convert to the highly active parent drug PA2789, and incorporating a cyclopropane-fused pyrrolidine (amine) at C-7 resulted in some of the most active analogues.

TL;DR: It is demonstrated that fosfomycin synergistically enhances the uptake of tobramycin, resulting in increased inhibition of protein synthesis and ultimately bacterial killing.

TL;DR: This work led to the discovery of 35, a highly selective inhibitor of PI3Kδ which displays an excellent pharmacokinetic profile and is efficacious in a rodent model of rheumatoid arthritis.

TL;DR: A case in which torsional scan studies guided the thoughtful creation of a restricted axis of rotation between two heteroaromatic systems of a phosphoinositide 3-kinase (PI3K) β inhibitor, generating a pair of atropisomeric compounds with significantly different pharmacological and pharmacokinetic profiles.