Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors: heterocyclic ring systems containing P1'and P2'substituents

J Kitchin, RC Bethell, N Cammack…

Index: Kitchin, John; Bethell, Richard C.; Cammack, Nicholas; Dolan, Simon; Evans, Derek N.; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 22 p. 3707 - 3716

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Citation Number: 21

Abstract

Reaction of racemic epoxide 6 with [3S-C3a, 4aa, 8aall-decahydro-N-(l, l-dimethylethyl~-3- isoquinolinecarboxamide gave diasteroisomers 34a and 34b. The stereochemistry of the hydroxyl grouping of 34a was determined to be (8). Reaction of the amines derived from 34a and 34b with thiazolidine 8a gave 50 and 51, respectively. Compound 50 was a potent inhibitor of HIV proteinase (IC50= 23 nM) with antiviral activity against HIV-1 in vitro (EC50 ...