Pyrazolopyrimidines as therapeutic agents

A compound of Formula (I)

• racemic-diastereomeric mixtures, optical isomers, pharmaceutically-acceptable salts or prodrugs thereof wherein:
• G is
• where Z100 is
• or a group optionally substituted with R1 selected from the group consisting of, cycloalkyl, naphthyl, tetrahydronaphthyl,
• benzothienyl, furanyl, thienyl, benzoxazolyl, benzothiazolyl,
• thiazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, indolyl, isoxazolyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl, pyrazolyl, pyrrolyl, oxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, indolinyl, indazolyl, benzoisothiazolyl, pyrido-oxazolyl, pyrido-thiazolyl, pyrimido-oxazolyl, pyrimido-thiazolyl and benzimidazolyl;
• Z110 is a covalent bond, or an optionally substituted (C1-C6) which is optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO2, COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl;
• Z111 is a covalent bond, an optionally substituted (C1-C6) or an optionally substituted —(CH2)n-cycloalkyl-(CH2)n—;
• where the optionally substituted groups are optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO2, COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl;
• Ra and R1 each represent one or more substituents for each occurrence independently selected from the group consisting of hydrogen, halogen, —CN, —NO2, —C(O)OH, —C(O)H, —OH, —C(O)O-alkyl, substituted or unsubstituted carboxamido, tetrazolyl, trifluoromethylcarbonylamino, trifluoromethylsulfonamido, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkynyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkyl, substituted or unsubstituted amido groups, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylthio, —Z105—C(O)N(R)2, —Z105—N(R)—C(O)—Z200, —Z105—N(R)—S(O)2—Z200, —Z105—N(R)—C(O)—N(R)—Z200, Rc and CH2ORc;
• where Rc for each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —CH2—NRdRe, —W—(CH2)t—NRdRe, —W—(CH2)t—O-alkyl, —W—(CH2)t—S-alkyl, or —W—(CH2)t—OH;
• Z105 for each occurrence is independently a covalent bond or (C1-C6);
• Z200 for each occurrence is independently a substituted or unsubstituted (C1-C6), substituted or unsubstituted phenyl or substituted or unsubstituted —(C1-C6)-phenyl;
• Rd and Re for each occurrence are independently H, alkyl, alkanoyl or SO2-alkyl;
• or Rd, Re and the nitrogen atom to which they are attached together form a five- or six-membered heterocyclic ring;
• t for each occurrence is independently an integer from 2 to 6;
• W for each occurrence is independently a direct bond or O, S, S(O), S(O)2, or NRf, wherein Rf for each occurrence is independently H or alkyl;
• or R1 is a substituted or unsubstituted carbocyclic or heterocyclic ring fused with ring 2;
• R3 is hydrogen, hydroxy, substituted or unsubstituted alkoxy;
• A is -, —O—;
• —S—;
• —S(O)p—;
• —N(R)—;
• —N(C(O)OR)—;
• —N(C(O)R)—;
• —N(SO2R)—;
• —CH2O—;
• —CH2S—;
• —CH2N(R)—;
• —CH(NR)—;
• —CH2N(C(O)R))—;
• —CH2N(C(O)OR)—;
• —CH2N(SO2R)—;
• —CH(NHR)—;
• —CH(NHC(O)R)—;
• —CH(NHSO2R)—;
• —CH(NHC(O)OR)—;
• —CH(OC(O)R)—;
• —CH(OC(O)NHR)—;
• —CH═CH—;
• —C(═NOR)—;
• —C(O)—;
• —CH(OR)—;
• —C(O)N(R)—;
• —N(R)C(O)—;
• —N(R)S(O)p—;
• —OC(O)N(R)—;
• —N(R)—C(O)—(CH2)n—N(R)—, —N(R)C(O)O—;
• —N(R)—(CH2)n+1—C(O)—, —S(O)pN(R)—;
• —O—(CR2)n+1—C(O)—, —O—(CR2)n+1—O—, —N(C(O)R)S(O)p—;
• —N(R)S(O)pN(R)—;
• —N(R)—C(O)—(CH2)n—O—, —C(O)N(R)C(O)—;
• —S(O)pN(R)C(O)—;
• —OS(O)pN(R)—;
• —N(R)S(O)pO—;
• —N(R)S(O)pC(O)—;
• —SOpN(C(O)R)—;
• —N(R)SOpN(R)—;
• —C(O)O—;
• —N(R)P(ORb)O—;
• —N(R)P(ORb)—;
• —N(R)P(O)(ORb)O—;
• —N(R)P(O)(ORb)—;
• —N(C(O)R)P(ORb)O—;
• —N(C(O)R)P(ORb)—;
• —N(C(O)R)P(O)(ORb)O—, or —N(C(O)R)P(ORb)—;
• where R for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl or substituted or unsubstituted aryl;
• Rb for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted aryl;
• p is 1 or 2;
• or in a phosphorus containing group, the nitrogen atom, the phosphorus atom, R and Rb together form a five- or six-membered heterocyclic ring;
• or
• A is NRSO2 and R, Ra and the nitrogen atom together form a substituted or unsubstituted five or-six-membered heterocyclic ring fused to ring 1;
• R2 is —Z101-Z102;
• Z101 is a covalent bond, —(C1-C6)—, —(C1-C6)— —O—, —(C1-C6)—C(O)—, —(C1-C6)— —C(O)O—, —(C1-C6)—C(O)—NH—, —(C1-C6)—C(O)—N((C1-C6))— or a substituted or unsubstituted phenyl group;
• Z102 is hydrogen;
• a substituted or unsubstituted alkyl group;
• a substituted or unsubstituted cycloalkyl group;
• a substituted or unsubstituted, saturated or unsaturated heterocyclic group;
• or a substituted or unsubstituted, saturated or unsaturated heterobicyclic group;
• said substituted heterocyclic and substituted heterobicyclic group having one or more substituents each independently selected from the group consisting of hydroxyl, cyano, substituted or unsubstituted alkoxy, substituted or unsubstituted sulfonamido, substituted or unsubstituted ureido, substituted or unsubstituted carboxamido, substituted or unsubstituted amino, oxo, a saturated, unsaturated or aromatic, substituted or unsubstituted heterocyclic group consisting of one or more nitrogen atoms, one or more oxygen atoms or a combination thereof wherein the nitrogen atoms are independently optionally substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl group;
• or
• R2 is a group of the formula —B—E, wherein B is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted azacycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkylsulfonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aminoalkylcarbonyl, hydroxy substituted or unsubstituted alkylene, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylenecarbonyl or substituted or unsubstituted aminoalkylcarbonyl group;
• and E is substituted or unsubstituted azacycloalkyl, substituted or unsubstituted azacycloalkylcarbonyl, substituted or unsubstituted azacycloalkylsulfonyl, substituted or unsubstituted azacycloalkylalkyl, substituted or unsubstituted heteroaryl-substituted or unsubstituted heteroarylcarbonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted azacycloalkylcarbonylamino, substituted or unsubstituted heteroarylcarbonylamino s or substituted or unsubstituted aryl;
• a is 1 and D1, G1, J1, L1 and M1 are each independently selected from the group consisting
• of CRa and N, provided that at least two of D1, G1, J1, L1 and M1 are CRa;
• or
• a is 0, and one of D1, G1, L1 and M1 is NRa, one of D1, G1, L1 and M1 is CRa and the remainder are independently selected from the group consisting of CRa and N, wherein Ra is as defined above;
• b is 1 and D2, G2, J2, L2 and M2 are each independently selected from the group consisting of CRa and N, provided that at least two of D2, G2, J2, L2 and M2 are CRa;
• or
• b is 0, and one of D2, G2, L2 and M2 is NRa, one of D2, G2, L2 and M2 is CRa and the remainder are independently selected from the group consisting of CRa and N, wherein Ra is as defined above;
• and
• n for each occurrence is independently an integer from 0 to 6.