Exploring neoglycoprotein assembly through native chemical ligation using neoglycopeptide thioesters prepared via N-->S acyl transfer.

Sugars and simplified oligosaccharide "mimics" can be joined with protein fragments at pre-defined sites using reliable chemical reactions such as thiol alkylation and Cu(I) catalysed azide/acetylene ligation (click chemistry). These fragments have the potential to be assembled into neoglycoprotein therapeutics using native chemical ligation.

Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides.

Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.

Antagonists of the human A(2A) adenosine receptor. 4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines.

Antagonism of the human A(2A) receptor has been implicated as a point of therapeutic intervention in the alleviation of the symptoms associated with Parkinson's disease. This is thought to occur, at least in part, by increasing the sensitivity of the dopaminergic neurons to the residual, depleted levels of striatal dopamine. We herein describe a novel series of functionalized triazolo[4,5-d]pyrimidine derivatives that display functional antagonism of the A(2A) receptor.

Synthesis of the penta-oxazole core of telomestatin in a convergent approach to poly-oxazole macrocycles.

A protocol for the construction of poly-oxazoles with consecutive 2,4'-linkages is described, and has afforded an efficient route to a penta-oxazole which demarcates a route to telomestatin and related macrocyclic poly-oxazole systems.