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 (IC50 = 1.6 × 10−5 M) was comparable with H+/K+-ATP enzyme inhibitor in vitro.

Graphical abstractWe have devolped a reverse method to synthesize benzimidazole derivatives that inhibits H+/K+-ATP enzymatic activity as potential proton pump inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide