Substituted Tricyclic Pyrazolo-Pyrimidine Compounds

A compound of formula A or A′:

• or a pharmaceutically acceptable salt, tautomer, prodrug, solvate, metabolite, polymorph, analog or derivative thereof, wherein:
• W, when linked to the ring structure with a double bond, is O, and when linked to the ring structure with a single bond, is hydrogen, unsubstituted C1-C6 alkyl, or substituted C1-C6 alkyl, wherein said alkyl is optionally substituted with one or more groups, each of which is independently selected from halogen, SH, OH, NO2, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, N[(C1-C6)alkyl]CO[(C1-C6)alkyl], NHCO(C1-C6)alkyl, CON[(C1-C6)alkyl]2, CONH(C1-C6)alkyl, and CN;
• X, when linked to the ring structure with a double bond, is O, and when linked to the ring structure with a single bond, is hydrogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, ORX1, or NRX2RX3, wherein said alkyl is optionally substituted with one or more groups, each of which is independently selected from halogen, SH, OH, NO2, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, CN, and OCF3;
• RX1, RX2, and RX3 are each independently selected from hydrogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C6-C10 aryl, and substituted C6-C10 aryl, wherein said alkyl or aryl is optionally substituted with one or more RX4;
• each RX4 is independently selected from halogen, SH, OH, NO2, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, CN, OCF3, C1-C6alkoxy, and unsubstituted C1-C6 alkyl;
• Y and Z are each independently selected from N and NRN2;
• RN2 is selected from hydrogen and unsubstituted C1-C6 alkyl;
• R1 and R2 are each independently selected from hydrogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, substituted C2-C6 alkenyl, and (CH2)0-3-T1, wherein said alkyl or alkenyl is optionally substituted with one or more R4;
• or R1 and R2, taken together with the nitrogen atom to which they are attached form a unsubstituted heterocycle comprising one, two, or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, or substituted heterocycle comprising one, two, or three 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said heterocycle is optionally substituted with one or more R6;
• T1 is selected from unsubstituted C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl, unsubstituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, substituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, unsubstituted C6-C10 aryl, and substituted C6-C10 aryl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said cycloalkyl, heterocycle, aryl, or heteroaryl is optionally substituted with one or more R4;
• R3 is selected from unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, substituted C2-C6 alkenyl, unsubstituted C6-C15 aryl, substituted C6-C15 aryl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, unsubstituted C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl, unsubstituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and substituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, or heterocycle is optionally substituted with one or more R9;
• each R4 is independently selected from halogen, SH, OH, NO2, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, CN, OCF3, CF3, CH2F, CHF2, COOH, SO2NH2, C1-C6 alkoxy, C6-C10 aryloxy, unsubstituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, unsubstituted C6-C10 aryl, substituted C6-C10 aryl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, unsubstituted C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl, unsubstituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and substituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said aryl, heteroaryl, cycloalkyl, or heterocycle is optionally substituted with one or more R5;
• each R5 is independently selected from halogen, C1-C6 alkoxy, C6-C10 aryloxy, and unsubstituted C6-C10 aryl;
• each R6 is independently selected from unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, substituted C2-C6 alkenyl, unsubstituted C6-C10 aryl, substituted C6-C10 aryl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said alkyl, alkenyl, aryl, and heteroaryl is optionally substituted with one or more R7;
• each R7 is independently selected from unsubstituted C6-C10 aryl and substituted C6-C10 aryl, wherein said aryl is optionally substituted with one or more R8;
• each R8 is independently selected from halogen, OH, NO2, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, CN, CF3, CH2F, CHF2, COOH, SO2NH2, C1-C6 alkoxy, unsubstituted C1-C6 alkyl, and unsubstituted C2-C6 alkenyl;
• each R9 is independently selected from unsubstituted C6-C10 aryl, substituted C6-C10 aryl, halogen, OH, NO2, COOH, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, OCF3, CF3, CH2F, CHF2, CN, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, unsubstituted C3-C10 cycloalkyl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, C1-C6 alkoxy, C6-C10 aryloxy, and S(C1-C6) alkyl, wherein said alkyl or aryl is optionally substituted with one or more R10;
• each R10 is independently selected from halogen, OH, NO2, COOH, CF3, OCF3, CH2F, CHF2, C1-C6 alkoxy, unsubstituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, C1-C6 alkoxy, C6-C10 aryloxy, S(C1-C6 alkyl), unsubstituted C6-C10 aryl, CN, NH2, NH(C1-C6 alkyl), N[(C1-C6 alkyl)]2, NHC(O)O-Q-T, and NHC(O)-Q-T;
• Q is (CH2)0-6;
• T is selected from halogen, OH, NH2, N[(C1-C6)alkyl]2, NH(C1-C6)alkyl, NHC(O)(C1-C6)alkyl, unsubstituted C6-C10 aryl, substituted C6-C10 aryl, unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, unsubstituted C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl, unsubstituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and substituted heterocycle comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, wherein said aryl, cycloalkyl, heteroaryl, or heterocycle is optionally substituted with one or more R12;
• each R12 is independently selected from halogen, OH, NO2, unsubstituted C1-C6 alkyl, CF3, unsubstituted C1-C6 alkoxy, C6-C10 aryloxy, CN, NH2, NH(C1-C6 alkyl), and N[(C1-C6 alkyl)]2;
• and
• RS is hydrogen or unsubstituted or substituted C1-C6 alkyl.