Indinavir design/discovery

One of the successful examples of employment of QSAR in the design and development of an HIV drug is the discovery of Indinavir (L-735,524) (2), one of the first HIVPI approved by the US-FDA. Holloway et aL [163] first reported this compound when they conducted SAR studies on a combined series of isostere derivatives of (43,44). A high correlation between the inter-molecular interaction energy ( int) calculated for HIVPR inhibitor complexes and enzyme inhibition activity was observed. QSAR 51-53 were developed for native, acetylpepstatin-inhibited and L-689,502-inhibited HIVPR, respectively [ 163]. X-ray coordinates and the force field technique were employed in the calculation of int (intermolecular interaction energy). In these QSAR, rev is the cross-validated correlation coefficient. 

---