Journal of Medicinal Chemistry p. 295 - 303 (1987)
Update date:2022-07-31
Topics:
Jones
Venuti
Alvarez
Bruno
Berks
Prince
Evaluation of a series of lactam heterocyclic analogues of cilostamide as inhibitors of cyclic AMP phosphodiesterase derived from both human platelets and rat heart in comparison with their corresponding methoxy-substituted heterocycles has revealed that the N-cyclohexyl-N-methyl-4-oxybutyramide side chain of 2 is an important lipophilic and/or steric pharmacophore. Attachment of this side chain to the parent heterocycle of the potent cyclic AMP phosphodiesterase inhibitor anagrelide afforded the hybrid structure RS-82856, shown to be more potent than either of its progenitors as an inhibitor of cyclic AMP phosphodiesterase or of ADP-induced platelet aggregation. The available in vitro data suggest that 1 possesses potentially useful antithrombotic and cardiotonic properties.
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