Dorzolamide A Success Story of Structure-Based Drug Design

In our view, the work described above is a very nice example for structure-based design. The key to success is the use of all available structural information and an early consideration of the physicochemical properties. 

The described work has also significant impact on the design of inhibitors for other enzymes. The first published nonpeptidic inhibitors of the cysteine protease interleukin converting enzyme (ICE) have been designed following the Zeneca approach [12]. Similarly, thrombin inhibitors have recently been disclosed that were designed along the same lines [13]. 

3 Dorzolamide A Success Story of Structure-Based Drug Design 

The application of structure-based design has already contributed significantly to the discovery of marketed drugs. We would like emphasize this point by briefly summarizing some structural aspects in the discovery of the carbonic anhydrase inhibitor dorzolamide [14,15]. 

The ACE-inhibitor captopril is frequently quoted as the first example of a drug which was obtained from structure-based design. Indeed, in the paper describing the discovery of captopril, Cushman and coworkers emphasize the value of their active site model of ACE in the design of captopril [16], As the 3D structure of ACE was not known by Cushman, the work 

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