Topical carbonic anhydrase inhibitors.
Ethoxzolamide and several derivatives (1-6) were synthesized and evaluated for carbonic anhydrase inhibition (CAI), solubility, pKa, distribution, and corneal permeability. The 6-hydroxy (5) and, particularly, the 6-chloro (6) analogues have the best combination of properties for penetrating the site of action and reducing intraocular pressure. Both 5 and 6 exhibited topical effectiveness in the normal rabbit, with 6 showing greater potency.
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D005016:Ethoxzolamide / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005901:Glaucoma / Q000188:drug therapy; D011817:Rabbits; D013844:Thiazoles / Q000627:therapeutic use*
D002257:Carbonic Anhydrase Inhibitors; D013844:Thiazoles; D005016:Ethoxzolamide