Medivir Ab

Janssen R&d Ireland

Bjorn Olaf Classon

Bengt Bertil Samuelsson

Kenneth Simmen

Hans Kristian Wallberg

Ingemar Sven-Anders Kvarnstrom

Karl Magnus Milsson

Susana Ayesa Alverez

Herman Agustinus De Kock

Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or stereoisomers thereof, wherein the dashed line, X, R, R, R, R, R, R, and Rhave defined meanings; the preparation thereof; compositions containing compounds of formula (I), including bioavailable combinations with ritonavir; and the pharmaceutical uses thereof.

Macrocyclic inhibitors of hepatitis C virus

Compounds of formula (I), wherein A&prime; and A&Prime; are independently the same or different group of formula (II) wherein: R&prime; is H, CH , C(CH ) , &mdash;OR , &mdash;N(R ) , &mdash;N(R )OR or &mdash;DP; R&prime;&Prime; is H or CH ; R is H, C -C alkyl; D is a bond, alkylene, &mdash;C(&boxH;O)&mdash;, &mdash;S(O)&mdash; or S(O) &mdash;; P is an optionally substituted, mono or bicyclic carbo- or hetereocycle; R&Prime; is H, any of the sidechains found in the natural amino acids, carboxacetamide, or a group (CH ) DP; M is a bond or &mdash;C(&boxH;O)N(R&prime;&Prime;)&mdash;; Q is absent, a bond, &mdash;CH(OH)&mdash; or CH &mdash;; or R&Prime; together with Q, M and R&prime; 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&prime; is &mdash;OR , &mdash;, N(R ) , &mdash;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&prime; and Z&Prime; are independently &mdash;(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.

Antiviral protease inhibitors

Growing community of inventors

Stockholm, Sweden

Bjorn Olaf Classon