Novel tricyclic compounds

The use of a compound of Formula 2:

• to form a compound of Formula (Ia)
• pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
• Rp is a hydrogen, —SO2N(CH3)2, —SO2(2,4,6-trimethylphenyl), —SO2phenyl, —SO2(4-butylphenyl), —SO2(4-methylphenyl), —SO2(4-methoxyphenyl), —C(O)OCH2CCl3, —C(O)OCH2CH2Si(CH3)3, —C(O)OC(CH3)3, —C(O)OC(CH3)2(CCl3), —C(O)O-1-adamantyl, —CH═CH2, —CH2CH2Cl, —CH(OCH2CH3)CH3, —CH2CH2-2-pyridyl, —CH2CH2-4-pyridyl, —Si(C(CH3)3)(CH3)2, —Si(CH(CH3)2)3, —CH2phenyl, —CH2(4-CH3O-phenyl), —CH2(3,4-di-methoxyphenyl), —CH2(2-nitrophenyl), -(2,4-dinitrophenyl), —CH2C(O)phenyl, —C(phenyl)3, —CH(phenyl)2, —C(phenyl)2(4-pyridyl), —N(CH3)2, —CH2OH, —CH2OCH3, —CH(OCH2CH3)2, —CH2OCH2CH2Cl, —CH2OCH2CH2Si(CH3)3, —CH2OC(CH3)3, —CH2OC(O)C(CH3)3, —CH2OCH2phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl)2;
• R1, R2 and R5 are each independently hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)(Rb), —C(O)Ra, —C(OH)RaRb, —N(Ra)S(O)2—Rb, —S(O)2N(Ra)(Rb), —CF3, —OCF3, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C1-C10) heterocyclyl, or optionally substituted (C6-C10)aryl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or optionally substituted (C1-C10)heteroaryl linked through a nitrogen;
• R3 is hydrogen, an optionally substituted bridged (C5-C12)cycloalkyl, optionally substituted bridged (C2-C10)heterocyclyl, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl;
• or
• R3 is -A-D-E-G, wherein:
• A is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• D is an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• E is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —ReC(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—OC(O)—Re, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• E is
• where in all cases, E is linked to either a carbon or a nitrogen atom in D;
• G is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —OC(O)N(Ra), —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted —(C1-C6)alkyl, an optionally substituted —(C2-C6)alkenyl, an optionally substituted —(C2-C6)alkynyl, an optionally substituted —(C3-C10)cycloalkyl, an optionally substituted —(C1-C10)heteroaryl, an optionally substituted —(C1-C10) heterocyclyl, an optionally substituted —(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• Ra and Rb are each independently hydrogen, deuterium, an optionally substituted (C1-C10)alkyl, an optionally substituted (C2-C10)alkenyl, an optionally substituted (C2-C10)alkynyl, an optionally substituted (C1-C10)alkyl-O—(C1-C10)alkyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C6-C10)aryl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10)heterocyclyl, an optionally substituted —(C1-C6)alkylene-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkylene-(C6-C10)aryl, an optionally substituted —(C1-C6)alkylene-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkylene-(C1-C10)heterocyclyl;
• and
• Re for each occurrence is independently a bond, an optionally substituted (C1-C10)alkylene, an optionally substituted (C2-C10)alkenylene, an optionally substituted (C2-C10)alkynylene, an optionally substituted —(C1-C10)alkylene-O—(C1-C10)alkylene group, an optionally substituted (C3-C10)cycloalkylene, an optionally substituted (C6-C10)arylene, an optionally substituted (C1-C10)heteroarylene, or an optionally substituted (C1-C10)heterocyclylene.

The use of a compound of Formula 3:

• to form a compound of Formula (Ib)
• pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
• Rp is a hydrogen, —SO2N(CH3)2, —SO2(2,4,6-trimethylphenyl), —SO2phenyl, —SO2(4-butylphenyl), —SO2(4-methylphenyl), —SO2(4-methoxyphenyl), —C(O)OCH2CCl3, —C(O)OCH2CH2Si(CH3)3, —C(O)OC(CH3)3, —C(O)OC(CH3)2(CCl3), —C(O)O-1-adamantyl, —CH═CH2, —CH2CH2Cl, —CH(OCH2CH3)CH3, —CH2CH2-2-pyridyl, —CH2CH2-4-pyridyl, —Si(C(CH3)3)(CH3)2, —Si(CH(CH3)2)3, —CH2phenyl, —CH2(4-CH3O-phenyl), —CH2(3,4-di-methoxyphenyl), —CH2(2-nitrophenyl), -(2,4-dinitrophenyl), —CH2C(O)phenyl, —C(phenyl)3, —CH(phenyl)2, —C(phenyl)2(4-pyridyl), —N(CH3)2, —CH2OH, —CH2OCH3, —CH(OCH2CH3)2, —CH2OCH2CH2Cl, —CH2OCH2CH2Si(CH3)3, —CH2OC(CH3)3, —CH2OC(O)C(CH3)3, —CH2OCH2phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl)2;
• R1, R2 and R5 are each independently hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)(Rb), —C(O)Ra, —C(OH)RaRb, —N(Ra)S(O)2—Rb, —S(O)2N(Ra)(Rb), —CF3, —OCF3, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C1-C10) heterocyclyl, or optionally substituted (C6-C10)aryl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or optionally substituted (C1-C10)heteroaryl linked through a nitrogen;
• R3 is hydrogen, an optionally substituted bridged (C5-C12)cycloalkyl, optionally substituted bridged (C2-C10)heterocyclyl, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl;
• or
• R3 is -A-D-E-G, wherein:
• A is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• D is an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• E is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —ReC(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—OC(O)—Re, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• E is
• where in all cases, E is linked to either a carbon or a nitrogen atom in D;
• G is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —OC(O)N(Ra), —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted —(C1-C6)alkyl, an optionally substituted —(C2-C6)alkenyl, an optionally substituted —(C2-C6)alkynyl, an optionally substituted —(C3-C10)cycloalkyl, an optionally substituted —(C1-C10)heteroaryl, an optionally substituted —(C1-C10) heterocyclyl, an optionally substituted —(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• R6 is a hydrogen, halogen, deuterium, an optionally substituted bridged (C5-C12)cycloalkyl group, optionally substituted bridged (C2-C10)heterocyclyl group, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl or -J-L-M-Q;
• wherein:
• J is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• L is a bond, an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• M is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—OC(O)—Re, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —Re—C(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• M is
• where in all cases, M is linked to either a carbon or a nitrogen atom in L;
• Q is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10) heterocyclyl, an optionally substituted (C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• Ra and Rb are each independently hydrogen, deuterium, an optionally substituted (C1-C10)alkyl, an optionally substituted (C2-C10)alkenyl, an optionally substituted (C2-C10)alkynyl, an optionally substituted (C1-C10)alkyl-O—(C1-C10)alkyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C6-C10)aryl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10)heterocyclyl, an optionally substituted —(C1-C6)alkylene-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkylene-(C6-C10)aryl, an optionally substituted —(C1-C6)alkylene-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkylene-(C1-C10)heterocyclyl;
• and
• Re for each occurrence is independently a bond, an optionally substituted (C1-C10)alkylene, an optionally substituted (C2-C10)alkenylene, an optionally substituted (C2-C10)alkynylene, an optionally substituted —(C1-C10)alkylene-O—(C1-C10)alkylene group, an optionally substituted (C3-C10)cycloalkylene, an optionally substituted (C6-C10)arylene, an optionally substituted (C1-C10)heteroarylene, or an optionally substituted (C1-C10)heterocyclylene.

The use of a compound of Formula 4:

• to form a compound of Formula (Ic)
• pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
• Rp1 is hydrogen, —SO2N(CH3)2, —SO2(2,4,6-trimethylphenyl), —SO2phenyl, —SO2(4-butylphenyl), —SO2(4-methylphenyl), —SO2(4-methoxyphenyl), —C(O)OCH2CCl3, —C(O)OCH2CH2Si(CH3)3, —C(O)OC(CH3)3, —C(O)OC(CH3)2(CCl3), —C(O)O-1-adamantyl, —CH═CH2, —CH2CH2Cl, —CH(OCH2CH3)CH3, —CH2CH2-2-pyridyl, —CH2CH2-4-pyridyl, —Si(C(CH3)3)(CH3)2, —Si(CH(CH3)2)3, —CH2phenyl, —CH2(4-CH3O-phenyl), —CH2(3,4-di-methoxyphenyl), —CH2(2-nitrophenyl), -(2,4-dinitrophenyl), —CH2C(O)phenyl, —C(phenyl)3, —CH(phenyl)2, —C(phenyl)2(4-pyridyl), —N(CH3)2, —CH2OH, —CH2OCH3, —CH(OCH2CH3)2, —CH2OCH2CH2Cl, —CH2OCH2CH2Si(CH3)3, —CH2OC(CH3)3, —CH2OC(O)C(CH3)3, —CH2OCH2phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl)2;
• Rp2 is hydrogen, —C(O)O—C(CH3)3, —C(O)OCH2-phenyl, —C(O)O-fluoren-9-yl, —C(O)CH3, —C(O)CF3, —C(O)—CH(CH3)2, —CH2-phenyl, —CH2-(4-methoxyphenyl), —S(O)2-phenyl or —S(O)2-(4-methylphenyl);
• R1, R2 and R5 are each independently hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)(Rb), —C(O)Ra, —C(OH)RaRb, —N(Ra)S(O)2—Rb, —S(O)2N(Ra)(Rb), —CF3, —OCF3, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C1-C10) heterocyclyl, or optionally substituted (C6-C10)aryl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or optionally substituted (C1-C10)heteroaryl linked through a nitrogen;
• R3 is hydrogen, an optionally substituted bridged (C5-C12)cycloalkyl, optionally substituted bridged (C2-C10)heterocyclyl, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl;
• or
• R3 is -A-D-E-G, wherein:
• A is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• D is an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• E is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —ReC(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—OC(O)—Re, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• E is
• where in all cases, E is linked to either a carbon or a nitrogen atom in D;
• G is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —OC(O)N(Ra), —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted —(C1-C6)alkyl, an optionally substituted —(C2-C6)alkenyl, an optionally substituted —(C2-C6)alkynyl, an optionally substituted —(C3-C10)cycloalkyl, an optionally substituted —(C1-C10)heteroaryl, an optionally substituted —(C1-C10) heterocyclyl, an optionally substituted —(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• R4 is a hydrogen, halogen, deuterium, an optionally substituted bridged (C5-C12)cycloalkyl group, optionally substituted bridged (C2-C10)heterocyclyl group, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl or -J-L-M-Q;
• wherein:
• J is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• L is a bond, an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• M is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—OC(O)—Re, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —Re—C(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• M is
• where in all cases, M is linked to either a carbon or a nitrogen atom in L;
• Q is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10) heterocyclyl, an optionally substituted (C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• Ra and Rb are each independently hydrogen, deuterium, an optionally substituted (C1-C10)alkyl, an optionally substituted (C2-C10)alkenyl, an optionally substituted (C2-C10)alkynyl, an optionally substituted (C1-C10)alkyl-O—(C1-C10)alkyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C6-C10)aryl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10)heterocyclyl, an optionally substituted —(C1-C6)alkylene-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkylene-(C6-C10)aryl, an optionally substituted —(C1-C6)alkylene-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkylene-(C1-C10)heterocyclyl;
• and
• Re for each occurrence is independently a bond, an optionally substituted (C1-C10)alkylene, an optionally substituted (C2-C10)alkenylene, an optionally substituted (C2-C10)alkynylene, an optionally substituted —(C1-C10)alkylene-O—(C1-C10)alkylene group, an optionally substituted (C3-C10)cycloalkylene, an optionally substituted (C6-C10)arylene, an optionally substituted (C1-C10)heteroarylene, or an optionally substituted (C1-C10)heterocyclylene.

The use of a compound of Formula 5

• to form a compound of Formula (Id)
• pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
• Rp is hydrogen, —SO2N(CH3)2, —SO2(2,4,6-trimethylphenyl), —SO2phenyl, —SO2(4-butylphenyl), —SO2(4-methylphenyl), —SO2(4-methoxyphenyl), —C(O)OCH2CCl3, —C(O)OCH2CH2Si(CH3)3, —C(O)OC(CH3)3, —C(O)OC(CH3)2(CCl3), —C(O)O-1-adamantyl, —CH═CH2, —CH2CH2Cl, —CH(OCH2CH3)CH3, —CH2CH2-2-pyridyl, —CH2CH2-4-pyridyl, —Si(C(CH3)3)(CH3)2, —Si(CH(CH3)2)3, —CH2-phenyl, —CH2(4-CH3O-phenyl), —CH2(3,4-di-methoxyphenyl), —CH2(2-nitrophenyl), -(2,4-dinitrophenyl), —CH2C(O)phenyl, —C(phenyl)3, —CH(phenyl)2, —C(phenyl)2(4-pyridyl), —N(CH3)2, —CH2OH, —CH2OCH3, —CH(OCH2CH3)2, —CH2OCH2CH2Cl, —CH2OCH2CH2Si(CH3)3, —CH2OC(CH3)3, —CH2OC(O)C(CH3)3, —CH2OCH2phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl)2;
• R1, R2 and R5 are each independently hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)(Rb), —C(O)Ra, —C(OH)RaRb, —N(Ra)S(O)2—Rb, —S(O)2N(Ra)(Rb), —CF3, —OCF3, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C1-C10) heterocyclyl, or optionally substituted (C6-C10)aryl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or optionally substituted (C1-C10)heteroaryl linked through a nitrogen;
• R3 is hydrogen, an optionally substituted bridged (C5-C12)cycloalkyl, optionally substituted bridged (C2-C10)heterocyclyl, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl;
• or
• R3 is -A-D-E-G, wherein:
• A is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• D is an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• E is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —ReC(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—OC(O)—Re, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• E is
• where in all cases, E is linked to either a carbon or a nitrogen atom in D;
• G is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —OC(O)N(Ra), —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted —(C1-C6)alkyl, an optionally substituted —(C2-C6)alkenyl, an optionally substituted —(C2-C6)alkynyl, an optionally substituted —(C3-C10)cycloalkyl, an optionally substituted —(C1-C10)heteroaryl, an optionally substituted —(C1-C10) heterocyclyl, an optionally substituted —(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• R4 and R6 are each independently a hydrogen, halogen, deuterium, an optionally substituted bridged (C5-C12)cycloalkyl group, optionally substituted bridged (C2-C10)heterocyclyl group, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl or -J-L-M-Q;
• wherein:
• J is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• L is a bond, an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C6-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• M is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—OC(O)—Re, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —Re—C(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• M is
• where in all cases, M is linked to either a carbon or a nitrogen atom in L;
• Q is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10) heterocyclyl, an optionally substituted (C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• Ra and Rb are each independently hydrogen, deuterium, an optionally substituted (C1-C10)alkyl, an optionally substituted (C2-C10)alkenyl, an optionally substituted (C2-C10)alkynyl, an optionally substituted (C1-C10)alkyl-O—(C1-C10)alkyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C6-C10)aryl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10)heterocyclyl, an optionally substituted —(C1-C6)alkylene-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkylene-(C6-C10)aryl, an optionally substituted —(C1-C6)alkylene-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkylene-(C1-C10)heterocyclyl;
• and
• Re for each occurrence is independently a bond, an optionally substituted (C1-C10)alkylene, an optionally substituted (C2-C10)alkenylene, an optionally substituted (C2-C10)alkynylene, an optionally substituted —(C1-C10)alkylene-O—(C1-C10)alkylene group, an optionally substituted (C3-C10)cycloalkylene, an optionally substituted (C6-C10)arylene, an optionally substituted (C1-C10)heteroarylene, or an optionally substituted (C1-C10)heterocyclylene.

The use of a compound of Formula 6

• to prepare a compound of Formula (Ig) or Formula (If) or Formula (Ii)
• pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein
• Rp is a hydrogen, —SO2N(CH3)2, —SO2(2,4,6-trimethylphenyl), —SO2phenyl, —SO2(4-butylphenyl), —SO2(4-methylphenyl), —SO2(4-methoxyphenyl), —C(O)OCH2CCl3, —C(O)OCH2CH2Si(CH3)3, —C(O)OC(CH3)3, —C(O)OC(CH3)2(CCl3), —C(O)O-1-adamantyl, —CH═CH2, —CH2CH2Cl, —CH(OCH2CH3)CH3, —CH2CH2-2-pyridyl, —CH2CH2-4-pyridyl, —Si(C(CH3)3)(CH3)2, —Si(CH(CH3)2)3, —CH2phenyl, —CH2(4-CH3O-phenyl), —CH2(3,4-di-methoxyphenyl), —CH2(2-nitrophenyl), -(2,4-dinitrophenyl), —CH2C(O)phenyl, —C(phenyl)3, —CH(phenyl)2, —C(phenyl)2(4-pyridyl), —N(CH3)2, —CH2OH, —CH2OCH3, —CH(OCH2CH3)2, —CH2OCH2CH2Cl, —CH2OCH2CH2Si(CH3)3, —CH2OC(CH3)3, —CH2OC(O)C(CH3)3, —CH2OCH2phenyl, -(2-tetrahydropyranyl), —C(O)H, or —P(S)(phenyl)2;
• Rx is a hydrogen, fluorine, chlorine, bromine, iodine, —OS(O)2CH3, —OS(O)2CF3, —OS(O)2phenyl, or —OS(O)2(4-methylphenyl);
• R1, R2 and R5 are each independently hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)(Rb), —C(O)Ra, —C(OH)RaRb, —N(Ra)S(O)2—Rb, —S(O)2N(Ra)(Rb), —CF3, —OCF3, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C1-C10) heterocyclyl, or optionally substituted (C6-C10)aryl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or optionally substituted (C1-C10)heteroaryl linked through a nitrogen;
• R3 is hydrogen, an optionally substituted bridged (C5-C12)cycloalkyl, optionally substituted bridged (C2-C10)heterocyclyl, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl;
• or
• R3 is -A-D-E-G, wherein:
• A is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• D is an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• E is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —ReC(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—OC(O)—Re, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• E is
• where in all cases, E is linked to either a carbon or a nitrogen atom in D;
• G is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —OC(O)N(Ra), —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted —(C1-C6)alkyl, an optionally substituted —(C2-C6)alkenyl, an optionally substituted —(C2-C6)alkynyl, an optionally substituted —(C3-C10)cycloalkyl, an optionally substituted —(C1-C10)heteroaryl, an optionally substituted —(C1-C10) heterocyclyl, an optionally substituted —(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• R6 is a hydrogen, halogen, deuterium, an optionally substituted bridged (C5-C12)cycloalkyl group, optionally substituted bridged (C2-C10)heterocyclyl group, optionally substituted (C1-C8)alkyl, optionally substituted (C3-C10)cycloalkyl, optionally substituted (C3-C8)cycloalkenyl, optionally substituted (C6-C10)aryl, optionally substituted (C1-C10)heteroaryl, optionally substituted (C2-C10)heterocyclyl or -J-L-M-Q;
• wherein:
• J is a bond, —C(O)—, optionally substituted (C1-C6)alkylene, optionally substituted (C2-C6)alkenylene, optionally substituted (C2-C6)alkynylene, optionally substituted (C3-C12)cycloalkylene, optionally substituted (C2-C6)heterocyclylene, —C(O)N(Ra)—Re—, —N(Ra)C(O)—Re—, —O—Re—, —N(Ra)—Re—, —S—Re—, —S(O)2—Re—, —S(O)Re—, —C(O—Ra)(Rb)—Re—, —S(O)2N(Ra)—Re—, —N(Ra)S(O)2—Re— or —N(Ra)C(O)N(Rb)—Re—;
• L is a bond, an optionally substituted (C1-C8)alkylene, optionally substituted bridged (C5-C12)cycloalkylene, optionally substituted (C3-C10)cycloalkylene, optionally substituted bridged (C5-C10)cycloalkenylene, optionally substituted (C3-C10)cycloalkenylene, optionally substituted (C6-C10)arylene, optionally substituted (C1-C10)heteroarylene, optionally substituted bridged (C2-C10)heterocyclylene or an optionally substituted (C2-C10)heterocyclylene;
• M is a bond, —Re—, —Re—C(O)—Re—, —Re—C(O)C(O)—Re—, —Re—C(O)O—Re—, —Re—OC(O)—Re, —Re—C(O)C(O)N(Ra)—Re—, —Re—N(Ra)—C(O)C(O)—Re—, —Re—O—Re—, —Re—S(O)2—Re—, —Re—S(O)—Re—, —Re—S—Re—, —Re—N(Ra)—Re—, —Re—N(Ra)C(O)—Re—, —Re—C(O)N(Ra)Re—, —Re—OC(O)N(Ra)—Re—, —Re—N(Ra)C(O)ORe—, —Re—N(Ra)C(O)N(Rb)—Re—, —Re—N(Ra)S(O)2—Re—, or —Re—S(O)2N(Ra)—Re—;
• or
• M is
• where in all cases, M is linked to either a carbon or a nitrogen atom in L;
• Q is hydrogen, deuterium, —N(Ra)(Rb), halogen, —ORa, —SRa, —S(O)Ra, —S(O)2Ra, —NO2, —C(O)ORa, —CN, —C(O)N(Ra)(Rb), —N(Ra)C(O)Rb, —N(Ra)C(O)ORb, —N(Ra)C(O)N(Rb)2, —C(O—Ra)(Rb)2, —C(O)Ra, —CF3, —OCF3, —N(Ra)S(O)2Rb, —S(O)2N(Ra)(Rb), —S(O)2N(Ra)C(O)Rb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10) heterocyclyl, an optionally substituted (C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkyl-(C6-C10)aryl, an optionally substituted —(C1-C6)alkyl-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkyl-(C1-C10)heterocyclyl;
• wherein in a moiety containing —N(Ra)(Rb), the nitrogen, Ra and Rb may form a ring such that —N(Ra)(Rb) represents an optionally substituted (C2-C10)heterocyclyl or an optionally substituted (C1-C10) heteroaryl linked through a nitrogen;
• Ra and Rb are each independently hydrogen, deuterium, an optionally substituted (C1-C10)alkyl, an optionally substituted (C2-C10)alkenyl, an optionally substituted (C2-C10)alkynyl, an optionally substituted (C1-C10)alkyl-O—(C1-C10)alkyl, an optionally substituted (C3-C10)cycloalkyl, an optionally substituted (C6-C10)aryl, an optionally substituted (C1-C10)heteroaryl, an optionally substituted (C1-C10)heterocyclyl, an optionally substituted —(C1-C6)alkylene-(C3-C10)cycloalkyl, an optionally substituted —(C1-C6)alkylene-(C6-C10)aryl, an optionally substituted —(C1-C6)alkylene-(C1-C10)heteroaryl, or an optionally substituted —(C1-C6)alkylene-(C1-C10)heterocyclyl;
• and
• Re for each occurrence is independently a bond, an optionally substituted (C1-C10)alkylene, an optionally substituted (C2-C10)alkenylene, an optionally substituted (C2-C10)alkynylene, an optionally substituted —(C1-C10)alkylene-O—(C1-C10)alkylene group, an optionally substituted (C3-C10)cycloalkylene, an optionally substituted (C6-C10)arylene, an optionally substituted (C1-C10)heteroarylene, or an optionally substituted (C1-C10)heterocyclylene.