Lithium Hexamethyldisilazane Transformation of Transiently Protected 4-Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated Imidazole Ring Formation.

Trimethylsilyl-transient protection successfully allowed the use of lithium hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI) amidines from nitriles in 58-88% yields. This strategy offers a much better choice to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and aldehydes was affected in dimethyl sulfoxide in 10-15 min, while known procedures require long time and purification. These methods are important for the BI/azaBI-based drug industry and for developing specific DNA binders for expanded therapeutic applications.

Synthesis and assessment of formamidines as new histamine H2-receptor antagonists.

Four series of compounds whose substructure contains a formamidine functionalized as a novel group in the chemistry of histamine H2-receptors have been synthesized. Series design, synthesis and pharmacological data including inhibition of histamine-stimulated acid secretion, inhibition of acid secretion p.o. and pA2 are reported. N-[(E)-[[2-[[[2](Diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide (ebrotidine, CAS 100981-43-9, FI-3542) was selected for further research.