Merck Sharp + Dohme Corp.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Instituto Di Ricerche Di Biologia Molecolare P. Angeletti

Msd Italia S.r.l.

Monica Donghi

Cristina Gardelli

Vincenzo Summa

Frank Narjes

Steven Harper

Malcolm MacCoss

Philippe L Durette

David Brian Olsen

Michael Rowley

Marco Ferrara

Uwe Koch

Olaf Kinzel

Benedetta Crescenzi

Barbara Pacini

Barbara Attenni

Malte Meppen

The present invention relates to macrocyclic compounds of formula (I): wherein W, n, m, R, R, R, R, R, R, M, Z and ring B are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus. 

Macrocyclic compounds as antiviral agents

The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention. (I) 

Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection

Pyridopyrimidine carboxamide compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein R, R, R, R, Rand Rare defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

HIV integrase inhibitors

The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention. 

Growing community of inventors

Rome, Italy

Monica Donghi