FACILE SYNTHESES OF C-2-SYMMETRICAL HIV-1 PROTEASE INHIBITORS

With the goal of obtaining inexpensive yet potent anti-AIDS drugs, sim ple inhibitors of HIV-1 protease were synthesised. The C-2-symmetrical pseudopeptidic substrate analogues can be prepared as inhibitors for HIV-1 protease starting from symmetrical ketones 3a-d by a facile four -step synthesis. After bromination of 3a-d to alpha,alpha'-dibromoketo nes 4a-d, we synthesised the diamino compounds 6a-c by Gabriel synthes is, which were then coupled with I Z-valine to yield inhibitors with a central keto group 2a-c. We also synthesised inhibitors including a c entral hydroxy group 8a-d a-i by azidation, reduction with LiAlH4 and coupling of the beta,beta'-diaminohydroxy compounds with appropriate p eptides, The first set of compounds showed only weak inhibition wherea s the latter reach K-i values of up to 3.0 mu M.