Pyrazolo[1,5-A] pyrimidine derivatives

A compound of formula I:

• wherein R1 is hydrogen, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl;
• R2 is hydrogen, halogen, —CN, —NO2, —CHO, -G-R7 [G is a bond, —C(═O)— or —O—C(═O)—;
• and R7 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, —OR8 (R8 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl), —NR9R10 (R9 is as defined for R8;
• R10 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl or —OCH3), —R11 (R11 is an optionally substituted saturated heterocyclyl with 5 to 7 members containing one to four heteroatoms selected from N, O and S), C6-C14 optionally substituted aryl or optionally substituted heteroaryl;
• provided that when R7 is C6-C14 optionally substituted aryl or optionally substituted heteroaryl, then G is not a bond], —NR9C(═O)R12 (R9 is as defined for R8;
• R12 is hydrogen, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl), —NR9C(═X)OR13 (R9 and R13, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR9C(═X)NR13R14 (R9 R13 and R14, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR9SO2R13 (R9 and R13, which may be the same or different, are as defined for R8), —SR9 (R9 is as defined for R8) or —S(O)mR9 (R9 is as defined for R8;
• m is 1 or 2);
• R3 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 unsubstituted aryl, C6-C14 substituted aryl [As substituents of C6-C14 aryl may be mentioned one or more selected from the group consisting of halogen, —CN, —NO2, —CHO, -G-R15 {G is a bond, —C(═O)— or —O—C(═O)—;
• R15 is C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, —OR16 (R16 is as defined for R8) or —NR17R18 (R17 and R18, which may be the same or different, are as defined for R8)}, —NR17C(═O)R19 (R17 is as defined for R8;
• R19 is as defined for R12), —NR17C(═X)OR18 (R17 and R18, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR17C(═X)NR18R20 R17, R18 and R20, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR17SO2R18 (R17 and R18, which may be the same or different, are as defined for R8), —S(O)mR17 (R17 is as defined for R8;
• m is 0, 1 or 2) and —SO2NR21R22 (R21 and R22, which may be the same or different, are as defined for R8;
• R21 and R22 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, —CN, —NO2, —CHO, -G-R23 {G is a bond, —C(═O)— or —O—C(═O)—;
• R23 is as defined for R15}, —NR24C(═O)R25 (R24 is as defined for R8;
• R25 is as defined for R12), —NR24C(═X)OR26 (R24 and R26, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR24C(═X)NR26R27 (R24, R26 and R27, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR24SO2R26 (wherein R24 and R26, which may be the same or different, are as defined for R8), —S(O)mR24 (R24 is as defined for R8;
• m is 0, 1 or 2) and —SO2NR28R29 (R28 and P29, which may be the same or different, are as defined for R8;
• R28 and R29 together may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said monocyclic or bicyclic heterocycle may optionally be substituted with one or more substituents)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl;
• R4 is hydrogen, halogen, C1-C8 optionally substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl, —OR30 (R30 is as defined for R8), —SR30 (R30 is as defined for R8), —NR30R31 (R30 and R31, which may be the same or different, are as defined for R8), —NR30C(═O)R32 (R30 is as defined for R8;
• and R32 is as defined for R12), —NR30C(═X)OR31 (R30 and R31, which may be the same or different, are as defined R8;
• X is O, S, N—CN or NH), —NR30C(═X)NR31R33 (R30, R31 and R33, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH) or —NR30SO2R31 (R30 and R31, which may be the same or different, are as defined for R8);
• R5 is C1-C8 substituted alkyl, C2-C8 optionally substituted alkenyl, C2-C8 optionally substituted alkynyl, C3-C8 substituted cycloalkyl [As substituents of C3-C8 cycloalkyl may be mentioned one or more selected from the group consisting of halogen, —CN, —NO2, —CHO, -G-R34 {G is a bond, —C(═O)— or —O—C(═O)—;
• R34 is as defined for R15}, —NR35C(═O)R36 (R35 is as defined for R8;
• R36 is as defined for R12), —NR35C(═X)OR37 (R35 and R37, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH ), —NR35C(═X)NR37R38 (R35, R37 and R38, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH) and —NR35SO2R37 (R35 and R37, which may be the same or different, are as defined for R8)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned one or more selected from the group consisting of halogen, —CN, —NO2, —CHO, -G-R39 {G is a bond, —C(═O)— or —O—C(═O)—;
• R39 is as defined for R15}, —NR40C(═O)R41 (R40 is as defined for R8;
• R41 is as defined for R12), —NR40C(═X)OR42 (R40 and R42, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR40C(═X)NR42R43 (R40, R42 and R43, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH) and —NR40SO2R42 (R40 and R42, which may be the same or different, are as defined for R8)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl, optionally substituted heterocyclylalkynyl or —NR44R45 (R44 and R45, which may be the same or different, are C1-C8 optionally substituted alkyl;
• R44 and R45 together may be taken together with the nitrogen to which they are attached to form a mono heterocycle with 5-7 members and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, the said mono heterocycle may optionally be substituted with one or more substituents);
• R6 is hydrogen, C1-C8 optionally substituted alkyl, C3-C8 optionally substituted cycloalkyl, C6-C14 optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted arylalkyl or optionally substituted heterocyclylalkyl;
• with the provisos:
• that R1, R2 and R4 are not all H;
• that R4 is not pentafluorophenyl;
• that R5 is not a group represented as the following (a):
• (a) C1-C6 alkyl or C3-C6 cycloalkyl, in which an alkyl group or a cycloalkyl group optionally may be substituted by phenyl or by one or more fluoro substituents;
• and pharmaceutically acceptable salts, and other pharmaceutically acceptable biohydrolyzable derivatives thereof, including esters, amides, carbamates, carbonates, ureides, solvates, hydrates, affinity reagents or prodrugs.