Novel spirocyclic pyrrolidones as P2/P1 mimetics in potent inhibitors of HIV-1 protease

We have developed concise and efficient syntheses of novel spirocyclic pyrrolidones 1-3, which involve the alkylation of pyrrolidone precursor 13 with 1.5-dibromopentane, 16 and 15, followed by an in situ lactamization. Conjugates of 1 and 2 with P1'/P2' hydroxy-indanolamine moiety resulted in novel and potent inhibitors of HTV-1 protease 25 and 26. suggesting that 1 and 2 are novel P2/P1 HIV-P1 mimetics. (C) 2002 Elsevier Science Ltd. All rights reserved.