Cyclic nucleotides, specifically cAMP and cGMP, are an integral piece in human signal transduction. Control of these nucleotides provides an opportunity to intervene in many disease states. A key to this control is inhibition of phosphodiesterases, enzymes that catalyze the hydrolysis of cAMP and cGMP. Among the phosphodiesterases family, the isozymes 3 and 4 have been implicated in heart disease and asthma. The crux of our diversity-oriented library synthesis was to develop a facile path for the production of potential phosphodiesterase inhibitors. In our efforts to prepare organic compounds as novel inhibitors specific for phosphodiesterases 3 and 4, we investigated four synthetic pathways. Central to our synthetic scheme was the coupling of seven heterocyclic amines to four different substrates. This synthesis proceeded through phenyl amines, keto acids, bicyclic lactams or dihydropyridazinones. Here we report that that secondary amines couple easily to bromobenzene, but not readily to dihydropyridazinones, .bicyclic lactams, and keto acids.
|School:||California State University, Long Beach|
|School Location:||United States -- California|
|Source:||MAI 52/05M(E), Masters Abstracts International|
|Subjects:||Chemistry, Biochemistry, Organic chemistry|
|Keywords:||Cyclic nucleotides, Medicinal chemistry, Organic synthesis|
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