Dorothy Levorse

TL;DR: A series of beta-substituted biarylphenylalanine amides synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes found a potent, orally active DPP-4 inhibitor with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models.

TL;DR: The discovery of vibegron, a potent and selective human β3-AR agonist for the treatment of overactive bladder (OAB), is described, which possesses improved druglike properties and an overall superior preclinical profile compared to MK-0634.

TL;DR: The pK(a) methods reported here can be used to support the SAR screen of cationic lipids for siRNA delivery, and the information revealed through studying the impact of pK (a) on the interaction between cationing lipids and cell membranes will contribute significantly to the design of more efficient si RNA delivery vehicles.

TL;DR: Inhibitors that contained halogenated biphenylylethyl residues at P1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n- butyl-1,5-pentane dioic acid 1-(alpha(S-tert-butylglycine methylamide) amide.

TL;DR: SAR and pharmacokinetic characterization of this series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry are presented.