Nicotinamide mononucleotide derivatives and use thereof in the treatment of viral infections

A compound of Formula (I) comprising:

• or a pharmaceutically acceptable salt or solvate thereof or prodrug thereof;
• wherein:
• X is selected from O, CH2, S, Se, CHF, CF2 et C═CH2;
• R1 is selected from H, azido, cyano, C1-C8 alkyl, C1-C8 thio-alkyl, C1-C8 heteroalkyl and OR;
• wherein R is selected from H and C1-C8 alkyl;
• R2, R3, R4 et R5 are independently selected from H, halogen, azido, cyano, hydroxyl, C1-C12 alkyl, C1-C12 thioalkyl, C1-C12 heteroalkyl, C1-C12 haloalkyl and OR;
• wherein R is selected from H, C1-C12 alkyl, C(O)(C1-C12)alkyl, C(O)NH(C1-C12)alkyl, C(O)O(C1-C12)alkyl, C(O)aryl, C(O)(C1-C12)alkyl aryl, C(O)NH(C1-C12)alkyl aryl, C(O)O(C1-C12)alkyl aryl and C(O)CHRAANH2;
• wherein RAA is a side chain selected from a proteinogenic amino acid;
• R6 is selected from H, azido, cyano, C1-C8 alkyl, C1-C8 thio-alkyl, C1-C8 heteroalkyl and OR;
• wherein R is selected from H and C1-C8 alkyl;
• R7 is selected from H, P(O)R9R10 et P(S)R9R10;
• wherein:
• R9 and R10 are independently selected from OH, OR11, NHR13, NR13R14, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl, C5-C12 aryl, C1-C8 arylalkyl, C1-C8 alkylaryl, C1-C8 heteroalkyl, C1-C8 heterocycloalkyl, heteroaryl and NHCRαRα′C(O)R12;
• wherein:
• R11 is selected from C1-C10 alkyl, C3-C10 cycloalkyl, C5-C12 aryl, C1-C10 alkylaryl, substituted C5-C12 aryl, C1-C10 heteroalkyl, C1-C10 haloalkyl, —(CH2)nC(O)(C1-C15)alkyl, —(CH2)nOC(O)(C1-C15)alkyl, —(CH2)nOC(O)O(C1-C15)alkyl, —(CH2)nSC(O)(C1-C15)alkyl, —(CH2)nC(O)O(C1-C15)alkyl and —(CH2)nC(O)O(C1-C15)alkyl aryl;
• wherein n is an integer selected from 1 to 8;
• and P(O)(OH)OP(O)(OH)2;
• R12 is selected from hydrogen, C1-C10 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, haloalkyl, C3-C10 cycloalkyl, C3-C10 cycloheteroalkyl, C5-C12 aryl, C1-C4 alkylaryl and C5-C12 heteroaryl;
• wherein said aryl or heteroaryl groups are optionally substituted by one or two groups selected from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy and cyano;
• R13 and R10 are independently selected from H, C1-C8 alkyl and C1-C8 alkyl-aryl;
• Rα and Rα′ are independently selected from an hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, thio-alkyl, hydroxylalkyl, alkylaryl and C5-C12 aryl, —(CH2)3NHC(═NH)NH2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl and a side chain selected from a proteinogenic or non-proteinogenic amino acid;
• wherein said aryl groups are optionally substituted with a group selected from hydroxyl, C1-C10 alkyl, C1-C6 alkoxy, halogen, nitro and cyano;
• or
• R9 and R10 together with the phosphorus atoms to which they are attached form a 6-membered ring wherein —R9—R10— represents —CH2—CH2—CHR—;
• wherein R is selected from hydrogen, C5-C6 aryl and C5-C6 heteroaryl, wherein said aryl or heteroaryl groups are optionally substituted by one or two groups selected from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy and cyano;
• or
• R9 and R10 together with the phosphorus atoms to which they are attached form a 6-membered ring wherein -R9-R10- represents —O—CH2-CH2-CHR—O—;
• wherein R is selected from hydrogen, C5-C6 aryl and C5-C6 heteroaryl, wherein said aryl or heteroaryl groups are optionally substituted by one or two groups selected from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy and cyano
• R8 is selected from H, OR, NHR15, NR15R16, NH—NHR13, SH, CN, N3 and halogen;
• wherein R15 and R16 are independently selected from H, C1-C8 alkyl and C1-C8 alkyl-aryl;
• Y is selected from CH, CH2, C(CH3)2 and CCH3;
• represents a single or double bond according to Y;
• and
• represents the alpha or beta anomer depending on the position of R1,
• or a compound of formula (Ia)
• or pharmaceutically acceptable salts and/or solvates thereof or prodrugs thereof, wherein:
• X′1 and X′2 are independently selected from O, CH2, S, Se, CHF, CF2 and C═CH2;
• R′1 and R′13 are independently selected from H, azido, cyano, C1-C8 alkyl, C1-C8 thio-alkyl, C1-C8 heteroalkyl and OR;
• wherein R is selected from H and C1-C8 alkyl;
• R′2, R′3, R′4, R′5, R′9, R′10, R′11, R′12 are independently selected from H, halogen, azido, cyano, hydroxyl, C1-C12 alkyl, C1-C12 thio-alkyl, C1-C12 heteroalkyl, C1-C12 haloalkyl and OR;
• wherein R is selected from H, C1-C12 alkyl, C(O)(C1-C12)alkyl, C(O)NH(C1-C12)alkyl, C(O)O(C1-C12)alkyl, C(O)aryl, C(O)(C1-C12)alkyl aryl, C(O)NH(C1-C12)alkyl aryl, C(O)O(C1-C12)alkyl aryl or C(O)CHRAANH2, wherein RAA is a side chain selected from a proteinogenic amino acid;
• R′6 and R′8 are independently selected from H, azido, cyano, C1-C8 alkyl and OR;
• wherein R is selected from H and C1-C8 alkyl;
• R′7 and R′14 are independently selected from H, OR, NHR, NRR′, NH—NHR, SH, CN, N3 and halogen;
• wherein R and R′ are each independently selected from H, C1-C8 alkyl, C1-C8 alkyl aryl;
• Y′1 and Y′2 are independently selected from CH, CH2, C(CH3)2 or CCH3;
• M′ is selected from H or a suitable counterion;
• represents a single or a double bound depending on Y′1 and Y′2;
• and
• represents the alpha or beta anomer depending on the position of R′1 and R′13, for use in the treatment and/or prevention of viral infections.