NOVEL INHIBITORS OF PROLYL 4-HYDROXYLASE .4. PYRIDINE-2-CARBOXYLIC ACID ANALOGS WITH ALTERNATIVE 2-SUBSTITUENTS

As part of a programme to discover new inhibitors of prolyl 4-hydroxylase we have tested a series of 2 substituted pyridines where the substituent is not a carboxylic acid. The 2 substituent has been varied from acid mimics through partially ionised groups to non ionised iron-chelating groups. The results indicate that the 2 carboxylate of pyridine 2-carboxylic acid, 3, can be successfully replaced by groups capable of forming a 5-ring chelate with enzyme-bound iron. Three compounds, 17, 18 and 19 are more potent than pyridine 2-carboxylic acid 3 and have been identified as potential new starting points for medicinal chemistry.