Design of a New Inhibitor

Fignie 4. Right superimposition of the crystal structures of 3 (cyan) and 4 (yellow). Left one of the two low energy MNDO conformations of the proposed naphthyl compound 5. 

Apart from the variation of the starting compound 3, which led to a number of highly potent inhibitors [4], we have also tried to design molecules that fit into the model but belong to different chemical classes and might serve as new leads. Structures and potential distributions of various molecules were calculated and compared to the model. Finally, compound 7 was found that fulfills both the geometric and the electronic requirements. As in the case of compounds 1,2 and 3, there seem to be only few similarities between 3 and 7 as long as only the 

We would like to note that besides our modeling approach a large number of compounds was synthesized according to classical chemical lead optimization [4], though no major improvement was achieved. Furthermore we would like to mention that our compounds are not ideal as they exhibit both inadequate bioavailability and resistance problems. We trust, however, that some of these problems may be overcome by future studies. 

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