Lasamide Containing Sulfonylpiperazines as Effective Agents for the Management of Glaucoma Associated Symptoms

A series of 2,4‐dichloro‐5‐{[4‐(phenylsulfonyl)piperazin‐1‐yl]carbonyl}benzenesulfonamides were designed and synthesized through amidation of Lasamide 1 with substituted piperazines. The newly obtained compounds demonstrated remarkable inhibition potency and selectivity for the human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) II isoform. Selected compounds 7 and 9 were investigated in an in vivo model of glaucoma and showed relevant performances, with the latter being able to last the effect up to 4 hours. The results herein reported are in sustainment of Lasamide derivatives as a new class of compounds potentially exploitable for the management of uncontrolled intra ocular pressure (IOP). Amidation of Lasamide with piperazines led to potent and selective inhibitors of the human Carbonic Anhydrase (hCA, EC: 4.2.1.1) II isoform, whose role in glaucoma has been longtime validated. Insight into the interaction with the enzyme was gained through in silico studies. Two compounds (7 and 9) were demonstrated to be efficient in lowering the uncontrolled intraocular pressure in in vivo glaucoma model in rabbits.