Nucleoside derivatives for treating hepatitis C virus infection

• Main Authors: KEICHER, JESSE D, LIEHR, SEBASTIAN JOHANNES REINHARD, DYATKINA, NATALIA B, HANSON, ERIC JASON, ROBERTS, CHRISTOPHER DON
• Format: Patent
• Language: English
• Published: 29.09.2006
• Edition: 7
• Subjects: CHEMISTRY; DERIVATIVES THEREOF; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SUGARS

A compound of the formula Ia is described, as well as its use for the treatment of hepatitis C virus in a mammal. R and R1 are independently selected from the group consisting of: hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl - provided that R and R1 are not both hydrogen; R2 is selected from the group consisting of: cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, acylamino, guanidino, amidino, thioacylamino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, -NR3R4 where R3 and R4 are joined to form, together with the nitrogen atom bond thereto, a heterocyclic, substituted heterocyclic, heteroaryl, or substituted heteroaryl; or -NR5NR3R4; W is selected from the group consisting of: hydrogen, phosphate, phosphonate, acyl, alkyl, sulfonate ester, a lipid, an amino acid, a carbohydrate, a peptide, and cholesterol; Y is selected from the group consisting of: hydrogen, halo, hydroxy, alkylthio, -NR3R4; Z is selected from the group consisting of: hydrogen, halo, hydroxy, alkyl, azido, -NR3R4, and -NR5NR3R4. A process of preparing a compound of Formula Ia is described to comprise coupling an optionally protected sugar to a purine base; or coupling an organometallic carbon nucleophile with a ketone which has been produced by oxidising an optionally protected nucleoside.