Nitrogenous Heterocyclic Derivatives And Their Application In Drugs

A compound of Formula (I):

• or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein:
• V1 is N or CR1, V2 is N or CR2, V3 is N or CR3, and V4 is N or CR4, wherein at most one of the V1, V2, V3 and V4 is N;
• X is a bond, NR5, O, S, C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene, —R6—C(═Y)—, —R6—C(═Y)—O—, —R6—C(═Y)—N(R5)—, —R6—S(═O)t—, —R6—S(═O)t—N(R7)—, or —R6—Y—, wherein each t is 1 or 2;
• Y is O or S;
• A is heterocyclylene, carbocyclylene, fused bicyclylene, fused heterobicyclylene, spiro bicyclylene, spiro heterobicyclylene, arylene or heteroarylene;
• B is alkoxy, hydroxy-substituted alkoxy, —NR7R7a, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7—S(═O)t—N(R7a)—, C4-12 carbocyclyl, C4-12 cycloalkyl, heterocyclyl, aryl, heteroaryl, fused bicyclyl, fused heterobicyclyl, spiro bicyclyl, or spiro heterobicyclyl;
• or A, X and B together form a group having Formula (II):
• wherein D is NR5, O, S, or CR7R7a;
• R1 is H, F, Cl, Br, I, cyano, hydroxy, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7S(═O)tN(R7a)—, R7aR7N-alkyl, R7S(═O)t-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)t-alkoxy, R7R7aN—C(═O)-alkoxy, aliphatic, haloalkyl, alkoxy, hydroxyalkoxy, aminoalkoxy, hydroxy-substituted aminoalkoxy, haloalkoxy, amino-substituted haloalkoxy, alkylaminohaloalkoxy, hydroxy-substituted haloalkoxy, alkylaminoalkoxy, alkoxyalkoxy, cycloalkyloxy, arylalkoxy, arylalkylamino, heteroarylalkoxy, heteroarylalkylamino, heterocyclylalkylamino, cycloalkylamino, heterocyclylalkoxy, carbocyclylalkoxy, carbocyclylalkylamino, heterocyclyl(hydroxyalkoxy), carbocyclyl(hydroxyalkoxy), aryl(hydroxyalkoxy), aryloxyalkoxy, aryloxy, heteroaryloxy, heteroaryloxyalkoxy, heterocyclyloxyalkoxy, carbocyclyloxyalkoxy, heterocyclyloxy, azidoalkoxy, fused bicyclyl, fused heterobicyclyl, fused bicyclyl aliphatic, fused heterobicyclyl aliphatic, fused bicycloxy, fused heterobicycloxy, fused bicyclylamino, fused heterobicyclylamino, fused bicyclylalkoxy, fused heterobicyclylalkoxy, fused bicyclylalkylamino, fused heterobicyclylalkylamino, fused bicycloxyalkoxy, fused heterobicycloxyalkoxy, fused bicyclylaminoalkoxy, fused heterobicyclylaminoalkoxy, fused bicyclyl-C(═O)—, fused bicyclyl-C(═O)O—, fused heterobicyclyl-C(═O)—, fused heterobicyclyl-C(═O)O—, fused bicyclylamino-C(═O)—, fused heterobicyclylamino-C(═O)—, fused bicyclyl-C(═O)N(R7)—, fused heterobicyclyl-C(═O)N(R7)—, spiro bicyclyl, spiro heterobicyclyl, spiro bicyclyl aliphatic, spiro heterobicyclyl aliphatic, spiro bicycloxy, spiro heterobicycloxy, spiro bicyclylamino, spiro heterobicyclylamino, spiro bicyclylalkoxy, spiro heterobicyclylalkoxy, spiro bicyclylalkylamino, spiro heterobicyclylalkylamino, spiro bicycloxyalkoxy, spiro heterobicycloxyalkoxy, spiro bicyclylaminoalkoxy, spiro heterobicyclylaminoalkoxy, spiro bicyclyl-C(═O)—, spiro bicyclyl-C(═O)O—, spiro heterobicyclyl-C(═O)—, spiro heterobicyclyl-C(═O)O—, spiro bicyclylamino-C(═O)—, spiro heterobicyclylamino-C(═O)—, spiro bicyclyl-C(═O)N(R7)—, spiro heterobicyclyl-C(═O)N(R7)—, heterocyclyl, cycloalkyl, aryl, heteroaryl, heterocyclyl aliphatic, cycloalkyl aliphatic, aryl aliphatic, heteroaryl aliphatic, aryl-(CH2)p-G-(CH2)m—, heteroaryl-(CH2)p-G-(CH2)m—, heterocyclyl-(CH2)p-G-(CH2)m—, or cycloalkyl-(CH2)p-G-(CH2)m—, wherein each G is O, S, NR5, S(═O), S(═O)2, C(═O), —C(═O)N(R7)—, —OC(═O)N(R7)—, —OC(═O)—, —N(R7)C(═O)N(R7)—, —(R7)N—S(═O)t—, —OS(═O)t—, or —OS(═O)tN(R7)—;
• each t is 1 or 2;
• each p and m is independently 0, 1, 2, 3 or 4;
• or wherein each of the C6-10 aryl-(CH2)p-G-(CH2)m—, C1-9 heteroaryl-(CH2)p-G-(CH2)m—, C2-10 heterocyclyl-(CH2)p-G-(CH2)m—, and C3-10 cycloalkyl-(CH2)p-G-(CH2)m— is optionally substituted by one or more F, Cl, Br, I, C1-6 alkyl, C2-6 alkynyl, C1-6 alkoxy or cyano;
• R2 is H, F, Cl, Br, I, cyano, hydroxy, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7S(═O)tN(R7a)—, R7aR7N-alkyl, R7S(═O)t-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)t-alkoxy, R7R7aN—C(═O)-alkoxy, aliphatic, haloalkyl, alkoxy, hydroxyalkoxy, aminoalkoxy, hydroxy-substituted aminoalkoxy, haloalkoxy, amino-substituted haloalkoxy, alkylaminohaloalkoxy, hydroxy-substituted haloalkoxy, alkylaminoalkoxy, alkoxyalkoxy, arylalkoxy, arylalkylamino, heteroarylalkoxy, heteroarylalkylamino, heterocyclylalkylamino, cycloalkyloxy, cycloalkylamino, heterocyclylalkoxy, carbocyclylalkoxy, carbocyclylalkylamino, heterocyclyl(hydroxyalkoxy), carbocyclyl(hydroxyalkoxy), aryl(hydroxyalkoxy), aryloxyalkoxy, aryloxy, heteroaryloxy, heteroaryloxyalkoxy, heterocyclyloxyalkoxy, carbocyclyloxyalkoxy, heterocyclyloxy, azidoalkoxy, fused bicyclyl, fused heterobicyclyl, fused bicyclyl aliphatic, fused heterobicyclyl aliphatic, fused bicycloxy, fused heterobicycloxy, fused bicyclylamino, fused heterobicyclylamino, fused bicyclylalkoxy, fused heterobicyclylalkoxy, fused bicyclylalkylamino, fused heterobicyclylalkylamino, fused bicycloxyalkoxy, fused heterobicycloxyalkoxy, fused bicyclylaminoalkoxy, fused heterobicyclylaminoalkoxy, fused bicyclyl-C(═O)—, fused bicyclyl-C(═O)O—, fused heterobicyclyl-C(═O)—, fused heterobicyclyl-C(═O)O—, fused bicyclylamino-C(═O)—, fused heterobicyclylamino-C(═O)—, fused bicyclyl-C(═O)N(R7)—, fused heterobicyclyl-C(═O)N(R7)—, spiro bicyclyl, spiro heterobicyclyl, spiro bicyclyl aliphatic, spiro heterobicyclyl aliphatic, spiro bicycloxy, spiro heterobicycloxy, spiro bicyclylamino, spiro heterobicyclylamino, spiro bicyclylalkoxy, spiro heterobicyclylalkoxy, spiro bicyclylalkylamino, spiro heterobicyclylalkylamino, spiro bicycloxyalkoxy, spiro heterobicycloxyalkoxy, spiro bicyclylaminoalkoxy, spiro heterobicyclylaminoalkoxy, spiro bicyclyl-C(═O)—, spiro bicyclyl-C(═O)O—, spiro heterobicyclyl-C(═O)—, spiro heterobicyclyl-C(═O)O—, spiro bicyclylamino-C(═O)—, spiro heterobicyclylamino-C(═O)—, spiro bicyclyl-C(═O)N(R7)—, spiro heterobicyclyl-C(═O)N(R7)—, heterocyclyl, cycloalkyl, aryl, C1-4 heteroaryl, heterocyclyl aliphatic, cycloalkyl aliphatic, aryl aliphatic, heteroaryl aliphatic, aryl-(CH2)p-G-(CH2)m—, heteroaryl-(CH2)p-G-(CH2)m—, heterocyclyl-(CH2)p-G-(CH2)m—, or cycloalkyl-(CH2)p-G-(CH2)m—, wherein each G is O, S, NR5, S(═O), S(═O)2, C(═O), —C(═O)N(R7)—, —OC(═O)N(R7)—, —OC(═O)—, —N(R7)C(═O)N(R7)—, —(R7)N—S(═O)t—, —OS(═O)t—, or —OS(═O)tN(R7)—;
• each t is 1 or 2;
• each p and m is independently 0, 1, 2, 3 or 4;
• R3 is H, F, Cl, I, cyano, R7R7aN—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7S(═O)tN(R7a)—, R7aR7N-alkyl, R7S(═O)t-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)t-alkoxy, R7R7aN—C(═O)-alkoxy, aliphatic, C2-10 haloalkyl, aryl-C2-10 alkoxy, heretoaryl-C3-10 alkoxy, cycloalkyl-C2-10 alkoxy, fused bicyclyl-C2-10 alkoxy, C1-4 heteroaryl, substituted aryl, heterocyclyl, cycloalkyl, heterocyclyl aliphatic, cycloalkyl aliphatic, C1-4 heteroaryl aliphatic, substituted aryl C3-10 alkyl, heterocyclylalkyl, alkoxy, hydroxyalkoxy, aminoalkoxy, hydroxy-substituted aminoalkoxy, haloalkoxy, amino-substituted haloalkoxy, alkylaminohaloalkoxy, hydroxy-substituted haloalkoxy, alkylaminoalkoxy, alkoxyalkoxy, aryl-C2-10 alkoxy, heterocyclylalkoxy, carbocyclylalkoxy, heterocyclyl(hydroxyalkoxy), carbocyclyl(hydroxyalkoxy), aryl(hydroxyalkoxy), aryloxyalkoxy, arylaminoalkoxy, aryloxy, heteroaryloxyalkoxy, heterocyclyloxyalkoxy, carbocyclyloxyalkoxy, heterocyclyloxy, cycloalkyloxy, azidoalkoxy, fused bicyclyl, fused heterobicyclyl, fused bicyclyl aliphatic, fused heterobicyclyl aliphatic, fused bicycloxy, fused heterobicycloxy, fused bicyclylamino, fused heterobicyclylamino, fused bicyclylalkoxy, fused heterobicyclylalkoxy, fused bicyclylalkylamino, fused heterobicyclylalkylamino, fused bicycloxyalkoxy, fused heterobicycloxyalkoxy, fused bicyclylaminoalkoxy, fused heterobicyclylaminoalkoxy, fused bicyclyl-C(═O)—, fused bicyclyl-C(═O)O—, fused heterobicyclyl-C(═O)—, fused heterobicyclyl-C(═O)O—, fused bicyclylamino-C(═O)—, fused heterobicyclylamino-C(═O)—, fused bicyclyl-C(═O)N(R7)—, fused heterobicyclyl-C(═O)N(R7)—, spiro bicyclyl, spiro heterobicyclyl, spiro bicyclyl aliphatic, spiro heterobicyclyl aliphatic, spiro bicycloxy, spiro heterobicycloxy, spiro bicyclylamino, spiro heterobicyclylamino, spiro bicyclylalkoxy, spiro heterobicyclylalkoxy, spiro bicyclylalkylamino, spiro heterobicyclylalkylamino, spiro bicycloxyalkoxy, spiro heterobicycloxyalkoxy, spiro bicyclylaminoalkoxy, spiro heterobicyclylaminoalkoxy, spiro bicyclyl-C(═O)—, spiro bicyclyl-C(═O)O—, spiro heterobicyclyl-C(═O)—, spiro heterobicyclyl-C(═O)O—, spiro bicyclylamino-C(═O)—, spiro heterobicyclylamino-C(═O)—, spiro bicyclyl-C(═O)N(R7)—, spiro heterobicyclyl-C(═O)N(R7)—, aryl-(CH2)p-G-(CH2)m—, heteroaryl-(CH2)p-G-(CH2)m—, heterocyclyl-(CH2)p-G-(CH2)m—, or cycloalkyl-(CH2)p-G-(CH2)m—, wherein each G is O, S, NR5, S(═O), S(═O)2, C(═O), —C(═O)N(R7)—, —OC(═O)N(R7)—, —OC(═O)—, —N(R7)C(═O)N(R7)—, —(R7)N—S(═O)t—, —OS(═O)t—, or —OS(═O)tN(R7)—;
• each t is 1 or 2;
• each p and m is independently 0, 1, 2, 3 or 4;
• R4 is H, F, I, cyano, hydroxy, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7S(═O)tN(R7a)—, R7aR7N-alkyl, R7S(═O)t-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)t-alkoxy, R7R7aN—C(═O)-alkoxy, aliphatic, haloalkyl, C2-10 alkoxy, hydroxyalkoxy, aminoalkoxy, hydroxy-substituted aminoalkoxy, haloalkoxy, amino-substituted haloalkoxy, alkylaminohaloalkoxy, hydroxy-substituted haloalkoxy, alkylaminoalkoxy, alkoxyalkoxy, C3-5 cycloalkyloxy, arylalkoxy, heteroarylalkoxy, heteroarylalkylamino, heterocyclylalkylamino, C7-10 cycloalkoxy, cycloalkylamino, heterocyclylalkoxy, carbocyclylalkoxy, carbocyclylalkylamino, heterocyclyl(hydroxyalkoxy), carbocyclyl(hydroxyalkoxy), aryl(hydroxyalkoxy), aryloxyalkoxy, aryloxy, heteroaryloxy, heteroaryloxyalkoxy, heterocyclyloxyalkoxy, carbocyclyloxyalkoxy, heterocyclyloxy, azidoalkoxy, fused bicyclyl, fused heterobicyclyl, fused bicyclyl aliphatic, fused heterobicyclyl aliphatic, fused bicycloxy, fused heterobicycloxy, fused bicyclylamino, fused heterobicyclylamino, fused bicyclylalkoxy, fused heterobicyclylalkoxy, fused bicyclylalkylamino, fused heterobicyclylalkylamino, fused bicycloxyalkoxy, fused heterobicycloxyalkoxy, fused bicyclylaminoalkoxy, fused heterobicyclylaminoalkoxy, fused bicyclyl-C(═O)—, fused bicyclyl-C(═O)O—, fused heterobicyclyl-C(═O)—, fused heterobicyclyl-C(═O)O—, fused bicyclylamino-C(═O)—, fused heterobicyclylamino-C(═O)—, fused bicyclyl-C(═O)N(R7)—, fused heterobicyclyl-C(═O)N(R7)—, spiro bicyclyl, spiro heterobicyclyl, spiro bicyclyl aliphatic, spiro heterobicyclyl aliphatic, spiro bicycloxy, spiro heterobicycloxy, spiro bicyclylamino, spiro heterobicyclylamino, spiro bicyclylalkoxy, spiro heterobicyclylalkoxy, spiro bicyclylalkylamino, spiro heterobicyclylalkylamino, spiro bicycloxyalkoxy, spiro heterobicycloxyalkoxy, spiro bicyclylaminoalkoxy, spiro heterobicyclylaminoalkoxy, spiro bicyclyl-C(═O)—, spiro bicyclyl-C(═O)O—, spiro heterobicyclyl-C(═O)—, spiro heterobicyclyl-C(═O)O—, spiro bicyclylamino-C(═O)—, spiro heterobicyclylamino-C(═O)—, spiro bicyclyl-C(═O)N(R7)—, spiro heterobicyclyl-C(═O)N(R7)—, heterocyclyl, cycloalkyl, aryl, heteroaryl, heterocyclyl aliphatic, cycloalkyl aliphatic, aryl C2-10 aliphatic, heteroaryl aliphatic, aryl-(CH2)p-G-(CH2)m—, heteroaryl-(CH2)p-G-(CH2)m—, heterocyclyl-(CH2)p-G-(CH2)m—, or cycloalkyl-(CH2)p-G-(CH2)m—, wherein each G is O, S, NR5, S(═O), S(═O)2, C(═O), —C(═O)N(R7)—, —OC(═O)N(R7)—, —OC(═O)—, —N(R7)C(═O)N(R7)—, —(R7)N—S(═O)t—, —OS(═O)t—, or —OS(═O)tN(R7)—;
• each t is 1 or 2;
• each p and m is independently 0, 1, 2, 3 or 4;
• each R5 is independently H, R7R7aNC(═O)—, R7OC(═O)—, R7C(═O)—, R7R7aNS(═O)—, R7OS(═O)—, R7S(═O)—, R7R7aNS(═O)2—, R7OS(═O)2—, R7S(═O)2—, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;
• each R5a is independently H, hydroxy, amino, F, Cl, Br, I, cyano, oxo (═O), R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)2—, R7S(═O)2—, R7S(═O)2N(R7a)—, R7aR7N-alkyl, R7S(═O)-alkyl, R7R7aN—C(═O)-alkyl, R7aR7N-alkoxy, R7S(═O)-alkoxy, R7R7aN—C(═O)-alkoxy, aryl, heteroaryl, alkoxy, alkyl, alkenyl, alkynyl, heterocyclyl, mercapto, nitro, aralkyl, arylamino, heteroarylamino, arylalkylamino, heteroarylalkylamino, heteroaryloxy, heteroarylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclyloxy, heterocyclylalkoxy, heterocyclylamino, heterocyclylalkylamino or aryloxy;
• each R6 is independently a bond, C1-10 alkylene, C2-10 alkenylene, or C2-10 alkynylene;
• and
• each R7 and R7a is independently H, aliphatic, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, arylaliphatic, heteroarylaliphatic, heterocyclylaliphatic, cycloalkylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, aryl, heteroaryl, heterocyclyl or carbocyclyl;
• with the proviso that where R7 and R7a are bonded to the same nitrogen atom, R7 and R7a, together with the nitrogen atom they are attached to, optionally form a substituted or unsubstituted 3-8 membered ring or a substituted or unsubstituted spiro bicyclic or fused bicyclic ring;
• wherein each of NR5, —R6—C(═Y)—, —R6—C(═Y)—O—, —R6—C(═Y)—N(R5)—, —R6—S(═O)t—, —R6—S(═O)t—N(R7)—, —R6—Y—, R7aR7N—, —C(═O)NR7R7a, —OC(═O)NR7R7a, —OC(═O)OR7, —N(R7)C(═O)NR7R7a, —N(R7)C(═O)OR7a, —N(R7)C(═O)—R7a, R7R7aN—S(═O)t—, R7S(═O)t—, R7S(═O)tN(R7a)—, R7aR7N-alkyl, R7S(═O)t-alkyl, R7R7aN—C(═O)—C1-6 alkyl, R7aR7N—C1-6 alkoxy, R7S(═O)-alkoxy, R7R7aN—C(═O)-alkoxy, R7R7aNC(═O)—, R7OC(═O)—, R7C(═O)—, R7R7aNS(═O)—, R7OS(═O)—, R7S(═O)—, R7R7aNS(═O)2—, R7OS(═O)2—, R7S(═O)2—, R7aR7N-aliphatic, aryl-(CH2)p-G-(CH2)m—, heteroaryl-(CH2)p-G-(CH2)m—, heterocyclyl-(CH2)p-G-(CH2)m—, cycloalkyl-(CH2)p-G-(CH2)m—, hydroxy-substituted C1-6 alkyl-C(═O)—, C1-6 alkyl-C(═O)—, C1-6 alkyl-S(═O)—, C1-6 alkyl-S(═O)2—, hydroxy-substituted C1-6 alkyl-S(═O)—, hydroxy-substituted C1-6 alkyl-S(═O)2—, carboxy C1-6 alkoxy, haloalkyl, heterocyclylalkyl, heterocyclylalkoxy, heterocyclylalkylamino, heterocyclylamino, cycloalkyl, cycloalkylaliphatic, cycloalkylamino, cycloalkyloxyaliphatic, cycloalkylalkoxy, cycloalkylalkylamino, carbocyclylaliphatic, aralkyl, aryloxyalkyl, heteroaryloxyaliphatic, aliphatic, alkoxy, hydroxyalkoxy, aminoalkoxy, hydroxy-substituted C1-6 alkoxy, hydroxy-substituted aminoalkoxy, haloalkoxy, amino-substituted haloalkoxy, alkylaminohaloalkoxy, hydroxy-substituted haloalkoxy, alkylaminoalkoxy, alkoxyalkoxy, arylalkoxy, arylalkylamino, heterocyclylalkoxy, carbocyclylalkoxy, heterocyclyl(hydroxyalkoxy), carbocyclyl(hydroxyalkoxy), aryl(hydroxyalkoxy), aryloxyalkoxy, heteroaryloxyalkoxy, aryloxy, arylamino, heterocyclyloxyalkoxy, carbocyclyloxyalkoxy, cycloalkyloxy, azidoalkoxy, fused bicyclyl, fused heterobicyclyl, fused bicyclyl aliphatic, fused heterobicyclyl aliphatic, fused bicycloxy, fused heterobicycloxy, fused bicyclylamino, fused heterobicyclylamino, fused bicyclylalkoxy, fused heterobicyclylalkoxy, fused bicyclylalkylamino, fused heterobicyclylalkylamino, fused bicycloxyalkoxy, fused heterobicycloxyalkoxy, fused bicyclylaminoalkoxy, fused heterobicyclylaminoalkoxy, fused bicyclyl-C(═O)—, fused bicyclyl-C(═O)O—, fused heterobicyclyl-C(═O)—, fused heterobicyclyl-C(═O)O—, fused bicyclylamino-C(═O)—, fused heterobicyclylamino-C(═O)—, fused bicyclyl-C(═O)N(R7)—, fused heterobicyclyl-C(═O)N(R7)—, spiro bicyclyl, spiro heterobicyclyl, spiro bicyclyl aliphatic, spiro heterobicyclyl aliphatic, spiro bicycloxy, spiro heterobicycloxy, spiro bicyclylamino, spiro heterobicyclylamino, spiro bicyclylalkoxy, spiro heterobicyclylalkoxy, spiro bicyclylalkylamino, spiro heterobicyclylalkylamino, spiro bicycloxyalkoxy, spiro heterobicycloxyalkoxy, spiro bicyclylaminoalkoxy, spiro heterobicyclylaminoalkoxy, spiro bicyclyl-C(═O)—, spiro bicyclyl-C(═O)O—, spiro heterobicyclyl-C(═O)—, spiro heterobicyclyl-C(═O)O—, spiro bicyclylamino-C(═O)—, spiro heterobicyclylamino-C(═O)—, spiro bicyclyl-C(═O)N(R7)—, spiro heterobicyclyl-C(═O)N(R7)—, aryl, heteroaryl, arylaliphatic, heteroarylaliphatic, heteroaryloxy, heteroarylamino, heteroarylalkoxy, heteroarylalkylamino, haloaliphatic, hydroxyaliphatic, aminoaliphatic, alkoxyaliphatic, alkylaminoaliphatic, alkylthioaliphatic, cycloalkyl, heterocyclylaliphatic, aryloxyaliphatic, heterocyclyloxyaliphatic, cycloalkyloxyaliphatic, arylaminoaliphatic, heterocyclylaminoaliphatic, cycloalkylaminoaliphatic, heterocyclyl, carbocyclyl, heterocyclylene, carbocyclylene, fused bicyclylene, fused heterobicyclylene, spiro bicyclylene, spiro heterobicyclylene, arylene and heteroarylene is unsubstituted or substituted with at least one substituent wherein the substituent is haloalkyl, oxo (═O), hydroxy, amino, F, Cl, Br, I, cyano, C1-10 alkoxy, C1-10 alkylamino, C1-10 alkylthio, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, mercapto, nitro, C6-10 aryl, C1-9 heteroaryl, C2-10 heterocyclyl, C6-10 aryloxy, carboxy, hydroxy-substituted C1-6 alkoxy, hydroxy-substituted C1-6 alkyl-C(═O)—, C1-6 alkyl-C(═O)—, C1-6 alkyl-S(═O)—, C1-6 alkyl-S(═O)2—, hydroxy-substituted C1-6 alkyl-S(═O)—, hydroxy-substituted C1-6 alkyl-S(═O)2—, or carboxyC1-6 alkoxy.