ChemInform Abstract: Substituted Xanthines, Pteridinediones, and Related Compounds as Potential Antiinflammatory Agents. Synthesis and Biological Evaluation of Inhibitors of Tumor Necrosis Factor α.
Abstract
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ChemInform Abstract
A series of analogues of pentoxifylline metabolites are prepared in the purine, pteridiene, (1,2,5)thiadiazolo(3,4-d)pyrimidine, and quinazoline ring systems of type (I)-(IV) and evaluated for their ability to inhibit the production of tumor necrosis factor-α ( TNFα) in human peripheral blood monocytes stimulated with bacterial lipopolysaccharide. The more active compounds are also tested for inhibition of cyclic AMP phosphodiesterase type IV (PDE IV) from human neutrophils. The compounds (Ia), (Ib), and (IIa) are the most potent compounds in the TNFα assay. Compound (IIa) is a very poor inhibitor of PDE IV but is the most active at preventing the leukopenia induced by TNFα in mice. Thus, compounds such as (IIa) , which are good inhibitors of TNFα production but are devoid of PDE IV inhibitory properties, may have potential as new antiinflammatory agents.
