Pyrazolo[1,5-a]pyrimidine derivatives

A compound of formula (I) and pharmaceutically acceptable salts, and other pharmaceutically acceptable biohydrolyzable derivatives thereof, including esters, aides, carbamates, carbonates, ureides, solvates, hydrates, affinity reagents or prodrugs:

• wherein R1 is hydrogen, C1-C8 optionally substituted alky, 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 single 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 heterocydlylalkenyl, 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), —R12 (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 single 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 arylal,yl optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted arylalkynyl or optionally substituted heterocyclylalkynyl), —NRC(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)NR13R14R (R9, R13 and R14, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR9SOR13 (R9 and R3, which may be the same or different, are as defined for R8) —SR9 (R9 is as defined for R8), or —S(O)nR9(R9 is as defined for R8;
• n 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 1 or 2 or more selected from the group consisting of halogen, —CN, —NO2, —CHO, —G—R15 {G is a single 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 R15, 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)OR8 (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 1 or 2 or more substituents)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned 1 or 2 or more selected from the group consisting of halogen, —CN, —NO2, —CHO, —G—R23 (G is a single 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 —SO2NR28R29R28 and R29, 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 1 or 2 or more substituents)], optionally substituted arylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkenyl, optionally substituted heterocyclylalkenyl, optionally substituted axylalkynyl or optionally substituted heterocyclylalkynyl;
• p1 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 heterocyclylakyl, 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 —NR3SO2R31 (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 1 or 2 or more selected from the group consisting of halogen, —CN, —NO2, —CHO, ═O, —G—R34 {G is a single bond, —C(═O)— or —O—C(═O)—;
• R34 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, —OR35 (R35 is as defined for R8) or N36R37 (R36 and R37, which may be the same or different, are as defined for R8)}, —NR38C(═O)R39 (R38 is as defined for R8;
• R39 is as defined for R12), —NR38C(═X)OR40 (R38 and R40, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH ), —NR38C(═X)NR40R41 (R38, R40 and R41, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH) and —NR38S2R40 (R38 and R40 hich may be the same or different, are as defined for R8)], unsubstituted heterocyclyl, substituted heterocyclyl [As substituents of heterocyclyl may be mentioned 1 or 2 or more selected from the group consisting of halogen, —CN, —NO2, —CHO, ═O, —G—R42 {G is a single bond, —C(—O)— or —O—C(═O)—;
• R42 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, —OR43 (R43 is as defined for R8) or —NR44R45 (R44 and R45, which may be the same or different, are as defined for R8)}, —NR46C(═O)R47 (R46 is as defined for R8;
• R47 is as defined for R12), —NR46C(═X)OR48 (R46 and R48, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH), —NR46C(═X)NR48R49 (R46, R48 and R49, which may be the same or different, are as defined for R8;
• X is O, S, N—CN or NH) and —NR46SO2R48 (R46 and R48, 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 or optionally substituted heterocyclylalkynyl;
• Y is —O— or —S—;
• provided that R5 is not C1-C6 alkyl which is unsubstituted or substituted (with 1 or 2 or more phenyls or halogens).