Studies on Griseolic Acid Derivatives. VI. : Synthesis and Phosphodiesterase-Inhibitory Activity of 6- and N¹-Substituted Derivatives of Griseolic Acid

Abstract

Twenty kinds of 6-substituted and five kinds of N¹-substituted griseolic acid derivatives were synthesized. The inhibitory activities of these compounds towards adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) phosphodiesterase (PDE) were investigated to clarify the structure-activity relationship. Substitution at the 6-position of griseolic acid caused a change of PDE IC₅₀ from 0.16 to 206μM against cAMP PDE. Substitution at the N¹-position also caused a change of PDE IC₅₀ from 0.16 to 127μM against cAMP PDE.