Antiviral protease inhibitors

Abstract

Compounds of formula (I), wherein A′ and A″ are independently the same or different group of formula (II) wherein: R′ is H, CH , C(CH ) , —OR , —N(R ) , —N(R )OR or —DP; R′″ is H or CH ; R is H, C -C alkyl; D is a bond, alkylene, —C(═O)—, —S(O)— or S(O) —; P is an optionally substituted, mono or bicyclic carbo- or hetereocycle; R″ is H, any of the sidechains found in the natural amino acids, carboxacetamide, or a group (CH ) DP; M is a bond or —C(═O)N(R′″)—; Q is absent, a bond, —CH(OH)— or CH —; or R″ together with Q, M and R′ define an optionally substituted 5 or 6 membered carbo- or heterocyclic ring which is optionally fused with a further 5 or 6 membered carbo- or heterocyclic ring; with the proviso that R′ is —OR , —, N(R ) , —N(R )OR or -DP, if M is a bond and Q is absent; X is H, OH, OCH , Y is H, OH, OCH , but X and Y are not both H; Z′ and Z″ are independently —(CH ) P where P is as defined above; n and m are independently 0, 1 or 2; and pharmaceutically acceptable salts and prodrugs thereof have utility as aspartyl protease inhibitors of HIV. They can be prepared in a facile two step synthesis from novel 2,5-di-O-benzyl-L-mannaro-1,4:6,3-dilactone intermediates.