gem-Dinitroalkyl Benzenes: A Novel Class of IOP-Lowering Agents for the Treatment of Ocular Hypertension.

Primary open angle glaucoma is the second most common cause of blindness worldwide. Nitric oxide has recently received particular attention as a potential antiglaucoma agent. In this work, gem-dinitroalkyl benzenes are evaluated for their capability to act as a new class of IOP lowering agents. These derivatives have been endowed with a variety of NO-release capacities and found to relax contracted rat aorta strips in a concentration-dependent manner. They have been studied for their IOP-lowering activity in a transient ocular hypertensive rabbit model at 1% dose. The most effective IOP-lowering products were compounds 9-11 and 13, whose activity was similar to that of Molsidomine 120 min after administration. Compounds 9 and 13 were selected for evaluation using carbomer-induced glaucoma as the chronic model of IOP. They cause a significant reduction in IOP in the first 24 h, and their activity is maintained over 5 days, displaying a Molsidomine-like profile.