Chemistry

A scalable, cobalt nanoparticle-based method for incorporating amine functional groups into drug-like molecules could facilitate drug production and the exploration of chemical space. The nanoparticles consist of a cobalt core encapsulated in a graphite shell, and catalyze a chemical reaction that reduces aldehyde or ketone groups to amine groups in the presence of ammonia or amine-containing fragment molecules. In a single-step reaction, the method converted aldehydes and ketones to primary, secondary or tertiary amines on diverse molecular scaffolds with yields of 78-92% and at scales up to 50 grams. The nanoparticles were used to synthesize 10 generic drugs, including the dual dopamine D2 receptor/D3 receptor (DRD3) agonist piribedil, the 3-ketoacyl-coA thiolase (kat-1) inhibitor trimetazidine and the appetite suppressant clobenzorex; and to add primary amines to several bioactive compounds, including the steroids androsterone and pregnenolone, the NSAID nabumetone and the vasodilator pentoxifylline, at similarly high yields. Next steps could include optimizing the nanoparticle or the method to improve compound yields.

Piribedil is marketed for Parkinson's disease and other neurological indications...