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. © 2011 Elsevier Ltd. All rights reserved.