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Improved anti-inflammatory PDE IV inhibitors The treatment of inflammatory diseases represents a major clinical challenge, perhaps the best example of which can be found in COPD (bronchitis and emphysema). In a recent dossier (Therapeutic and pharmaceutical approaches to COPD to access) we profiled the development of novel anti-inflammatories to treat this major and unmet disease. Some of the promising examples of new anti-inflammatories are the phosphodiesterase (PDE) IV inhibitors. Indeed in our report we highlighted three such molecules, Roflumilast, Arofylline and Cilomilast, each of which are in advanced clinical development. This class of drug is also in development for asthma, rheumatoid arthritis, multiple sclerosis and Crohn's disease. The development of improved inhibitors continues with a key aim being to reduce GI side effects. Recently, Janssen researchers reported a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described proved to be potent PDE4 inhibitors with impressive anti-inflammatory activity. Of greatest interest however is their less pronounced GI side effect profile and their further development is thus awaited with interest. Link to journal abstract:
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