Anti-viral drug

A method of treatment of positive-sense, single-stranded RNA (ssRNA) virus infection different from the West Nile Fever virus infection, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof to an subject in need thereof,

• wherein
• R1 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group;
• a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, an aryl group, an alkylaryl group, or a cycloheteroalkyl group having 3 to 12 carbon atoms;
• and
• the positive-sense, single-stranded ssRNA virus is a virus different from the West Nile Fever virus and is selected from the ssRNA viruses belonging to the Orders Nidovirales, Picornavirales, or Tymovirales;
• ssRNA viruses belonging to the unassigned families selected from the group consisting of Flaviviridae, Astroviridae, and Caliciviridae;
• wherein the Flaviviridae is selected from the group consisting of Hepacivirus, Pegivirus, Pestivirus, and Flavivirus, and wherein the Flavivirus is Zika virus.

A process for the manufacture of an antiviral compound of formula (I) or a pharmaceutically acceptable salt thereof

• wherein
• R1 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, an aryl group, an alkylaryl group, or a cycloheteroalkyl group having 3 to 12 carbon atoms,
• comprising the steps of:
• (a) diazotizing a compound of formula (II):
• wherein R2 is hydrogen, thereby forming a diazonium compound of formula (III) or a pharmaceutically acceptable salt thereof:
• (b) condensing the compound of formula (III) or a pharmaceutically acceptable salt thereof with at least one α-nitroester of formula (IV):
• wherein
• R3 is:
• —(CO)—OR5, wherein R5 is an alkyl group having 1 to 24 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group;
• —(CO)—R6, wherein R6 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group, or
• —O—(CO)—Y, wherein Y is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group;
• and
• R4 is an alkyl group having 1 to 24 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group;
• or an alkenyl group;
• thereby forming a compound of formula (I).

A process for the manufacture of an antiviral compound (A) of formula (I) or a pharmaceutically acceptable salt thereof

• wherein
• R1 is selected from an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, an aryl group, an alkylaryl group, or a cycloheteroalkyl group having 3 to 12 carbon atoms,
• comprising the steps of:
• (a) diazotizing a compound of formula (II):
• wherein R2 is equal to R1, as defined here above, thereby forming a diazonium compound of formula (III) or a pharmaceutically acceptable salt thereof:
• (b) condensing the diazonium compound of formula (III) or a pharmaceutically acceptable salt thereof, as obtained in step (a), with at least one α-nitroester of formula (IV):
• wherein R3 is:
• —(CO)—R6, wherein R6 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group, or
• —O—(CO)—Y, wherein Y is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group or an aralkyl group;
• and
• R4 is an alkyl group having 1 to 24 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group;
• or an alkenyl group.