A reverse method for diversity introduction of benzimidazole to synthesize H(+)/K(+)-ATP enzyme inhibitors.

A series of 2-[(2-pyridylmethyl)sulfinyl]benzimidazole derivatives were synthesized via a solution phase synthetic route using a reversal method of diversity introduction. Using this synthetic strategy, we obtained two key intermediates (4-A and 4-B) simultaneously, which allows us to introduce diversity points onto the benzimidazole part of the final product under reliable reaction conditions to identify potent H(+)/K(+)-ATP enzyme inhibitors. Compound 14l (IC(50)=1.6×10(-5)M) was comparable with H(+)/K(+)-ATP enzyme inhibitor in vitro.