CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE INHIBITION BY IMIDAZOPYRIDINES - ANALOGS OF SULMAZOLE AND ISOMAZOLE AS INHIBITORS OF THE CGMP SPECIFIC PHOSPHODIESTERASE

The synthesis and phosphodiesterase (PDE) inhibitory profile of a seri es of imidazopyridines, including sulmazole and isomazole, on separate d PDE isoenzymes are described. The results show that both sulmazole a nd isomazole are weak inhibitors of PDE III, and their inotropic activ ity is unlikely to be due to PDE III inhibition alone. Surprisingly, b oth compounds were found to be significant inhibitors of the cGMP spec ific isoenzyme, PDE V, and a series of simple 2-substituted phenylimid azo[4,5-b]pyridines have been made to investigate the SAR of PDE activ ity. This has been shown to be sensitive to chain length, polarity, an d the nature of the heteroatom linking group. Potent PDE V inhibitors, many of which are also significant inhibitors of PDE IV, have been id entified.