Bicyclic pyrazolo-heterocycles

A compound having the structure of formula I:

• or a pharmaceutically acceptable salt, acid salt, stereoisomer or hydrate thereof, wherein:
• the ring moiety A is selected from the group consisting of:
• wherein one of V, W, X, Y and Z is O and all others are each CH2;
• Ra is selected from the group consisting of C1-C8 alkyl, C3-C8 cycloalkyl, C4-C8 cycloalkenyl, (CH2)paryl, (CH2)p-linked 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl;
• wherein the C1-C8 alkyl, C3-C8 cycloalkyl, C4-C8 cycloalkenyl, aryl, 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl of Ra are each optionally substituted with one to four substituents independently selected from the group consisting of halo, OH, oxo, NH2, NO2, CN, COOH, OCF3, CF3, C1-C6 alkyl, C1-C4 alkoxy, C4-C8 alkenyl, C3-C6 cycloalkyl, aryl and 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl;
• Rb is selected from the group consisting of H, and C1-C6 alkyl optionally substituted with one to four substituents independently selected from the group consisting of C1-C4 alkoxy, halo, OH, NH2 and CN;
• Rc is CRdReRf;
• Rd is selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, (CH2)paryl, (CH2)p-linked 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl;
• wherein the C1-C6 alkyl, C3-C8 cycloalkyl, (CH2)paryl, (CH2)p-linked 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl of Rd are optionally substituted with one to four substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 hydroxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, aryl, halo, OH, NR1R2, CN, NO2, and CONR1R2;
• Re is selected from the group consisting of COR3, CONR3R4, CSNR3R4, COOR3, SOR3, SO2R3, SO2NR3R4, NR3SO2R4 and NR3COR4;
• Rf is selected from the group consisting of H, C1-C6 alkyl and C1-C8 hydroxyalkyl;
• each instance of R1 and R2 is independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C3-C8 alkynyl and C3-C8 cycloalkyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, C3-C8 alkynyl and C3-C8 cycloalkyl of each R1 and R2 is optionally substituted with one to four substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, OH, oxo, NO2, CN, OCF3, CF3, NR3R4, CONR3R4, COOR3, SOR3, SO2R3, SO2NR3R4, NR3COR4, and NR3SO2R4;
• R3 and R4 are each independently selected from the group consisting of H, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkoxyalkyl, C3-C8 cycloalkyl, C4-C8 cycloalkenyl, (CH2)paryl, (CH2)p-linked 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl;
• wherein the C1-C8 alkyl, C3-C8 cycloalkyl, C4-C8 cycloalkenyl, aryl, and 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl of R3 and R4 are each optionally substituted with one to four substituents independently selected from the group consisting of halo, OH, oxo, NR5R6, NO2, CN, OCF3, CF3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 hydroxyalkyl, CONR5R6, SOR5, SO2R5, SO2NR5R6, COOR5, NR5COR6 and NR5SO2R6;
• alternatively, R3 and R4 taken together with the nitrogen atom to which they are bonded form a heterocyclyl selected from the group consisting of 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl optionally substituted with one to four substituents independently selected from the group consisting of halo, OH, oxo, NR5R6, NO2, CN, OCF3, CF3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 hydroxyalkyl, CONR5R6, SOR5, SO2R5, SO2NR5R6, COOR5, NR5COR6 and NR5SO2R6;
• wherein each instance of R5 and R6 is independently selected from the group consisting of H, C1-C4 alkyl, aryl and 4-, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl, wherein the alkyl, aryl and heterocyclyl are each independently optionally substituted with one to three substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, OH, oxo, NO2, NH2, CN, OCF3 and CF3;
• and
• wherein each instance of p is independently 0 or an integer from 1 to 6.