Studies on anti-Helicobacter pylori agents. Part 1: Benzyloxyisoquinoline derivatives

The synthesis and optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives that was discovered by a random screening process, are described. In the in vitro assay, compound 10c containing a 3-acetamido-2,6-dichlorobenzyl substituent was found to ha ve extremely potent activity against H. pylori and no activity against othe r common bacteria. The anti-H. pylori activity of 10c was superior to that of amoxicillin (AMPC) (1) and clarithromycin (CAM) (2), However, 10c did no t show in vivo efficacy in a mouse infection model; a feature attributed to the lack of strong bactericidal activity at short contact times. (C) 1999 Elsevier Science Ltd. All rights reserved.