EARLY DAYS OF STRUCTURE-BASED DRUG DESIGN, THE TRUSOPT STORY Dr. Brian M. McKeever, Department of Biophysical Chemistry, Merck Research Laboratories, RY80M-136, 126 East Lincoln Ave., Rahway, N.J., 07065

Carbonic anhydrase (CA) has long been recognized as a potential therapeutic target for conditions involving the abnormal movement of fluid. As such, it was "targeted" for treatment of high intraocular pressure found in patients suffering from glaucoma. What was needed was not a powerful, specific enzyme inhibitor (that part was done), but a superior drug that could be safely bottled, delivered directly to the afflicted organ and lead to effortless patient compliance. CA was chosen as a model system for trying out a new approach to developing a compound to meet the clinical specifications, structure-based drug design.