Cyclic nucleotide phosphodiesterase inhibition by imidazopyridines: analogues of sulmazole and isomazole as inhibitors of the cGMP specific phosphodiesterase
| Autor: | Dashyant Dhanak, Brendan Connolly, Sean Thomas Flynn, Angela Worby, William J. Coates |
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| Rok vydání: | 1993 |
| Předmět: |
Phosphodiesterase Inhibitors
Pyridines Isozyme Amidine chemistry.chemical_compound Structure-Activity Relationship 3' 5'-Cyclic-GMP Phosphodiesterases Drug Discovery heterocyclic compounds chemistry.chemical_classification Bicyclic molecule Cyclic nucleotide phosphodiesterase biology Imidazoles Phosphodiesterase musculoskeletal system Isoenzymes enzymes and coenzymes (carbohydrates) Enzyme chemistry Biochemistry Enzyme inhibitor biology.protein Molecular Medicine sense organs PDE10A circulatory and respiratory physiology |
| Zdroj: | Journal of medicinal chemistry. 36(10) |
| ISSN: | 0022-2623 |
| Popis: | The synthesis and phosphodiesterase (PDE) inhibitory profile of a series of imidazopyridines, including sulmazole and isomazole, on separated PDE isoenzymes are described. The results show that both sulmazole and isomazole are weak inhibitors of PDE III, and their inotropic activity is unlikely to be due to PDE III inhibition alone. Surprisingly, both compounds were found to be significant inhibitors of the cGMP specific isoenzyme, PDE V, and a series of simple 2-substituted phenylimidazo[4,5-b]pyridines have been made to investigate the SAR of PDE activity. This has been shown to be sensitive to chain length, polarity, and the nature of the heteroatom linking group. Potent PDE V inhibitors, many of which are also significant inhibitors of PDE IV, have been identified. |
| Databáze: | OpenAIRE |
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