Medivir Ab

Ingemar Sven-Anders Kvarnstrom

Bengt Bertil Samuelsson

Bjorn Olof Classon

Bertil Samuelsson

Per-Ola Mikael Johansson

Lars Goran Svansson

Stefan Carl Svensson

Asa Rosenquist

Fredrik Thorstensson

Hans Kristian Wallberg

Susana Ayesa

Bjorn Olaf Classon

Laszlo Rakos

Hans Wallberg

Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site. 

HCV NS-3 serine protease inhibitors

Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site. 

Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus such as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

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

##STR1## Novel antiviral compounds of formulae (1A) and (1B), wherein X and R.sub.1 -R.sub.4 are as stated in claim 1 in the form of an .alpha.- or .beta.-anomer or a mixture thereof, and pharmaceutically acceptable salts thereof, are disclosed, as well as a new method for preparation thereof. Said compounds can be used for treatment of infections caused by viruses requiring reverse transcriptase for replication, such as HIV and hepatitis B virus.

Nucleoside derivatives

The instant disclosure is directed to cyclopentyl analogues of .alpha.- and .beta.-L-2', 3'-dideoxypurine ribonucleosides wherein the 3- and 4-cyclopentyl substituents may be either --H or --CH.sub.2 --OH.

Growing community of inventors

Linkoping, Sweden

Ingemar Sven-Anders Kvarnstrom