John Lawrence Lamattina

The impact of mergers on pharmaceutical R&D

Mergers and acquisitions in the pharmaceutical industry have substantially reduced the number of major companies over the past 15 years. The short-term business rationale for this extensive consolidation might have been reasonable, but at what cost to research and development productivity?

The synthetic utility of p-nitrophenyl 3-bromo-2,2-diethoxypropionate

Abstract The synthesis of p -nitrophenyl 3-bromo-2,2-diethoxypropionate, and its chemoselective reactions for the preparation of highly functionalized small molecules and also novel heterocycles, are described.

The reaction of 5-acetyl-2-aminooxazole with amines: an approach to 1H-5-acetyl-2-aminoimidazoles

Abstract 5-Acetyl-2-aminooxazole, upon treatment with amines in the presence of water, affords good yields of 1H-5-acetyl-2-substituted amino-imidazoles, along witn varying amounts of the corresponding 5-hydroxy-4-methyl-2-substituted aminopyrimidines.

A new route to 6-substituted 2,3-diaminopyridines

Abstract 2,3-Diaminopyridine reacts with cyclohexanone to form dihydro-4-azabenzimidazole-2-spirocyclohexane. Reaction of this intermediate with a variety of nucleophiles (e.g., water, phenylmercaptan, ethanol, dimethylamine, and diethylmalonate) in the presence of MnO 2 results in addition to the 5-position. Subsequent acidic hydrogenation affords 6-substituted-2,3-diaminopyridines, key synthons for the synthesis of bicyclic heterocycles.

A plan for sustainable funding for US biomedical research

The United States is facing two healthcare challenges — the equitable distribution of healthcare, and to support it, a sustainable biomedical research foundation for the discovery of new therapies and diagnostics. Although the US biomedical research infrastructure is currently strong, it is not a foregone conclusion that it will remain this way. As highlighted in a recent article1 (An audience with...Story Landis. Nature Rev. Drug Discov. 13, 718–719 (2014)), as well as by the American Society of Biochemistry and Molecular Biology2, federal funding for biomedical research in the United States has been decreasing for more than a decade (FIG. 1) and, considering the current political climate, the situation is likely to get even worse for at least the next few years. Over the same period, the private sector research and development (R&D) ecosystem in the United States has changed3. With increased globalization have come increased competition, pressure for short-term advantage and a shift in industry from early-stage research to later-stage development. This has resulted in increased offshoring of earlyand late-stage research efforts, with potential long-term negative consequences. Additionally, universities, research institutes and research hospitals have become more translationally focused and some have become proof-of-concept centres for new drug discovery ideas. These events have changed the dialogue between those who create biological knowledge and those who apply it, and suggest that successful drug R&D in the future will require new modes of interaction among academic, industrial and governmental organizations. Here, we propose a plan to help provide the funding needed to address the associated challenges: extending patents on drugs by one year and using the additional revenue to support biomedical R&D.

Synthesis of 2-amino-5-hydroxy-4-pyrimidones and 5,6-biheteroaryls using p-nitrophenyl 3-bromo-2,2-diethoxypropionate (NPBDP)

Abstract The reaction of NPBDP with various guanidines affords, after formic acid hydrolysis, 2-amino-5-hydroxy-4-pyrimidones. Reaction of NPBDP with o-aminoheterocycles gives similar results. NPBDP is readily converted to the 3-amino-2-alkenenitrile, 10, a key building block for the synthesis of 5,6-biheteroaryls.