Abstract
Replacement of the decahydroisoquinoline group contained in Ro 31-8959 by a cis-octahydrothienopyridine moiety has provided a high affinity hydroxyethylamine isostere for use in HIV-1 protease inhibitors. Further gains in potency have been realized by incorporation of a sulfur atom into the P 1 benzyl group. Modification by a key P 2 ligand provided LY316440, a potent, orally absorbed inhibitor of HIV-1 protease.
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