6-Nitrobenzimidazole derivatives: potential phosphodiesterase inhibitors: synthesis and structure-activity relationship.

ABSTRACT

6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 µM. Compounds 30 (IC(50)=1.5±0.043 µM), 1 (IC(50)=2.4±0.049 µM), 11 (IC(50)=5.7±0.113 µM), 13 (IC(50)=6.4±0.148 µM), 14 (IC(50)=10.5±0.51 µM), 9 (IC(50)=11.49±0.08 µM), 3 (IC(50)=63.1±1.48 µM), 10 (IC(50)=120.0±4.47 µM), and 6 (IC(50)=153.2±5.6 µM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 µM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.