Patent Evaluation: Pyrazopyrimidinones as phosphodiesterase inhibitors

Summary

Novelty: Novel pyrazolo[4,3-d]-pyrimidin-7-ones are disclosed which are inhibitors of cyclic guanosine 3′,5′-monophosphate phosphodiesterase. The compounds may have utility in the treatment of angina and hypertension.

Biology: Compound affinities for cGMP and cAMP PDE were determined in vitro using PDE enzymes isolated from rabbit platelets and rat kidney using the method of Thompson et al. (Biochemistry (1971) 10:311). Assays were performed using a modification of the method of Thompson and Appleman (Biochemistry (1979) 18:5228). Platelet anti-aggregatory activity was also assessed in vitro using standard turbidimetric techniques.

Chemistry: Synthesis was by standard techniques. Four compounds are exemplified by synthesis and all are specifically claimed. 1-Ethyl-5-(5-diethylsulphamoyl-2-n-propoxyphenyl)-3-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one is a preferred compound.