Inhibitors of influenza viruses replication

Abstract

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A compound is represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

1 . A method of inhibiting the replication of influenza viruses in a biological sample or patient, comprising the step of administering to said biological sample or patient an effective amount of a compound represented by the following structural formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Z 1  is —R*, —F, —Cl, —CN, —OR*, —CO 2 R*, —NO 2 , or —CON(R*) 2 ; 
 Z 2  is —R*, —OR*, —CO 2 R*, —NR* 2 , or —CON(R*) 2 ; 
 Z 3  is —H, —OH, halogen, —NH 2 ; —NH(C 1 -C 4  alkyl); —N(C 1 -C 4  alkyl) 2 , —O(C 1 -C 4  alkyl), or C 1 -C 6  alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
 R 1  is —H or C 1 -C 6  alkyl; 
 R 2  is —H; —F; —NH 2 ; —NH(C 1 -C 4  alkyl); —N(C 1 -C 4  alkyl) 2 ; —C═N—OH; cyclopropyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, —OCH 3 , and —CH 3 ; or C 1 -C 4  alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); and 
 R 3  is —H, —Cl, —F, —OH, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4 alkyl), —N(C 1 -C 4  alkyl) 2 , —Br, —CN, or C 1 -C 4  aliphatic that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (O—C 4  alkyl), and C 1 -C 4  alkoxy; 
 R 4  is: 
 
       
         
           
           
               
               
           
         
       
       wherein ring T is a C 3 -C 10  non-aromatic carbocycle optionally substituted with one or more instances of J A , or a 3-10 membered non-aromatic heterocycle optionally substituted with one or more instances of J B , or ring T and R 9  optionally form a non-aromatic C 5 -C 10  membered carbocycle optionally substituted with one or more instances of J A  or 5-10 membered non-aromatic heterocycle optionally substituted with one or more instances of J B ; 
       
         
           
           
               
               
           
         
       
       wherein ring J is a 3-10 membered non-aromatic heterocycle optionally substituted with one or more instances of J B ; or 
       
         
           
           
               
               
           
         
       
       wherein ring D is a 4-10 membered non-aromatic heterocycle optionally substituted with one or more instances of J D1 ; and
 each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, —NCO, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 4-8 membered ring that is optionally substituted with one or more instances of J E1 ; 
 Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 7 ) p —Y 1 —; 
 Y 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, —NRSO 2 NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, or —CO 2 SO 2 —; 
 R 5  is: i) —H; ii) a C 1 -C 6  aliphatic group optionally substituted with one or more instances of J C1 ; iii) a C 3 -C 10  non-aromatic carbocycle, or a 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of J C1 ; or iv) a 4-10 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of J p1 ; or 
 R 5 , together with Q 1 , optionally forms a 4-8 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; and 
 R 6  and R 7  are each independently —H or C 1 -C 6  alkyl optionally substituted with one or more substitutents selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6 hydroxyalkoxy and C 2 -C 6  alkoxyalkoxy, or optionally R 6  and R 7 , together with the carbon atom to which they are attached, form a cyclopropane ring optionally substituted with one or more instances of methyl; 
 R 9  is independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy and C 2 -C 6  alkoxyalkoxy; 
 R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring optionally substituted with one or more instances of methyl; 
 R and R′ are each independently —H or C 1 -C 6  alkyl optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy and C 2 -C 6 alkoxyalkoxy; or 
 
       optionally R′, together with R 5  and the nitrogen atom to which they are attached, forms a 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J D1 ;
 R* is independently: i) —H; ii) a C 1 -C 6  alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 3 -C 8  non-aromatic carbocycle, 5-6 membered non-aromatic heterocycle, phenyl, 5-6 membered heteroaryl, —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl); wherein each of said alkyl groups in —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl) is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and wherein each of said carbocycle, heterocycle, phenyl, and heteroaryl is independently and optionally substituted with one or more instances of J E1 ; or iii) a C 3 -C 8  non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is independently and optionally substituted with one or more instances of J E1 ; and 
 each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(═NR)R c , —C(═NR)NR b R c , —NRC(═NR)NR b R c , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , —NRSO 2 NR c R b , —P(O)(OR a ) 2 , —OP(O)(OR a ) 2 , —P(O) 2 OR a  and —CO 2 SO 2 R b , or optionally, two J C1  and two J D1 , respectively, together with the atom(s) to which they are attached, independently form a 4-8-membered ring that is optionally substituted with one or more instances of J E1 ; 
 each J E1  is independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl), wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and 
 R a  is independently: i) a C 1 -C 6  aliphatic group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, —O(C 1 -C 6  alkyl), —C(O)(C 1 -C 6 -alkyl), C 3 -C 8  non-aromatic carbocycle, 4-8 membered non-aromatic heterocycle, 5-10 membered heteroaryl group, and 6-10 membered carbocyclic aryl group; wherein each of said alkyl groups for the substituents of the C 1 -C 6  aliphatic group represented by R a  is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and wherein each of said carbocycle, heterocycle, heteroaryl and carbocyclic aryl groups for the substituents of the C 1 -C 6  aliphatic group represented by R a  is optionally and independently substituted with one or more instances of J E1 ; 
 
       ii) a C 3 -C 8  non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is optionally and independently substituted with one or more instances of J E1 ; or 
       iii) a 5-10 membered heteroaryl, or 6-10 membered carbocyclic aryl group, each of which is optionally and independently substituted with one or more instances of J E1 ; and
 R b  and R c  are each independently R a  or —H; or optionally, R b  and R c , together with the nitrogen atom(s) to which they are attached, each independently form a 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; 
 p is independently 1, 2, 3 or 4; 
 t is 0, 1 or 2; 
 j is 1 or 2; and 
 z is 1 or 2. 
 
     
     
         2 . The method of  claim 1 , represented by Structural Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 2 , wherein R 1  is —H. 
     
     
         4 . The method of  claim 3 , wherein R 2  is —H, —F, —CH 3 , —CH 2 OH, or —NH 2 . 
     
     
         5 . The method of  claim 4 , wherein R 2  is —H or —CH 3 . 
     
     
         6 . The method of  claim 5 , wherein R 3  is —H, —Cl, —F, —Br, —CN, —CF 3 , —O(C 1 -C 4  alkyl), —OH, —NH 2 , —NH(C 1 -C 4  alkyl) or —N(C 1 -C 4  alkyl) 2 . 
     
     
         7 . The method of  claim 6 , wherein R 4  is: 
       
         
           
           
               
               
           
         
       
       and wherein:
 ring A is a C 3 -C 10  non-aromatic carbocycle optionally further substituted with one or more instances of J A  or a 3-10 membered non-aromatic heterocycle optionally further substituted with one or more instances of J B ; 
 rings B and C are each independently a 4-10 membered non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ; 
 ring D is a 4-10 membered non-aromatic heterocycle optionally substituted with one or more instances of J D1 ; or 
 ring A and R 8  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 9  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 11  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, wherein each carbocycle is optionally further substituted with one or more instances of J A , and wherein each heteroocycle is optionally further substituted with one or more instances of J B , 
 Q 2  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 2 ) p —Y 1 —; 
 Q 3  is independently a bond, —C(O)—, —C(═NR)—, —C(═NR)NR—, —CO 2 —, —C(O)NR′—, —SO 2 —, —SO 2 NR′—, —C(O)NRC(O)O—, or —(CR 6 R 7 ) p —Y 1 —; 
 optionally, each Q 2  and Q 3 , together with R 5 , independently form a 5-7 membered ring optionally substituted with one or more instances of J E1 ; 
 R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; or R 8 , together with Q 2  and R 5 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; 
 R 10  is independently —H or a C 1 -C 6  alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, C 2 -C 6  alkoxyalkoxy, C 3 -C 8  non-aromatic carbocycle, phenyl, a 4-8 membered non-aromatic heterocycle, and a 5-6 membered heteroaryl group, wherein each of said carbocycle, phenyl, heterocycle and heteroaryl group is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
 n, m and k are each independently 0, 1 or 2; 
 x and y are each independently 0, 1 or 2; and 
 z is 1 or 2. 
 
     
     
         8 . The method of  claim 7 , wherein:
 n and m are each independently 0 or 1 when rings A and B are 3-6 membered; or n and m are each independently 0, 1 or 2 when rings A and B are 7-10 membered;   provided that if Y 1  is a bond, then R 5  is neither H nor a C 1-6  aliphatic group; and   provided that if each Q 2  and Q 3  independently is a bond, then R 5  is neither —H nor a C 1-6  aliphatic group.   
     
     
         9 . The method of  claim 8 , wherein:
 ring A is a C 3 -C 8  non-aromatic carbocycle or heterocycle, the carbocycle and heterocycle optionally further substituted with one or more instances of J A  and J B , respectively;   rings B and C are each independently a 4-8 membered non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ;   ring D is a 4-8 membered non-aromatic heterocycle optionally substituted with one or more instances of J D1 ;   Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, or —(CR 6 R 7 ) p —Y 1 —;   Q 2  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, or —(CR 6 R 7 ) p —Y 1 —;   Q 3  is independently a bond, —C(O)—, —C(═NR)—, —CO 2 —, —C(O)NR′—, —SO 2 —, —SO 2 NR′—, —C(O)NRC(O)O—, or —(CR 6 R 7 ) p —Y 1 —;   optionally, each of Q 2  and Q 3 , together with R 5 , independently forms a 5-7 membered ring optionally substituted with one or more instances of J E1 ;   Y 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—;   R 5  is: i) —H; ii) a C 1 -C 6  aliphatic group optionally substituted with one or more instances of J C1 ; iii) a C 3 -C 8  non-aromatic carbocycle, or a 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of J C1 ; or iv) a 4-8 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of J D1 ; or   R 5 , together with Q 1 , optionally forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; and   R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy;   R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy;   each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, —NCO, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 5-7 membered ring that is optionally substituted with one or more instances of J E1 ; and   each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , —NRSO 2 NR c R b , and —P(O)(OR a ) 2 , or optionally, two J C1  and two J D1 , respectively, together with the atoms to which they are attached, independently form a 5-7-membered ring that is optionally substituted with one or more instances of J E1 , and fused to the respective ring to which they are attached.   
     
     
         10 . The method of  claim 9 , wherein:
 ring A is a C 3 -C 8  non-aromatic carbocycle optionally and independently is further substituted with one or more instances of J A ;   rings B and C are each independently a 4-8 membered non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ;   ring D is a 4-8 membered non-aromatic heterocycle optionally substituted with one or more instances of J p1 ;   Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, or —(CR 6 R 2 ) p —Y 1 —;   Q 2  is independently bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 NR′—, —NRSO 2 NR′—, or —(CR 6 R 2 ) p —Y 1 —;   Q 3  is independently a bond, —C(O)—, —CO 2 —, —C(O)NR′—, —SO 2 —, —SO 2 NR′—, —C(O)NRC(O)O—, or —(CR 6 R 2 ) p —Y 1 —;   optionally, each of Q 2  and Q 3 , together with R 5 , independently forms a 5-7 membered ring optionally substituted with one or more instances of J E1 ;   Y 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—;   each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 5-7 membered ring that is optionally substituted with one or more instances of J E1  and fused to the ring to which they are attached; and   each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , and —NRSO 2 NR c R b , or optionally, two J C1  and two J D1 , respectively, together with the atoms to which they are attached, independently form a 5-7-membered ring that is optionally substituted with one or more instances of J E1 , and fused to the respective ring to which they are attached.   
     
     
         11 . The method of  claim 10 , wherein:
 Z 1  is —H, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), —F, —Cl, —CN, —CO 2 H, —CO 2 (C 1 -C 6  alkyl), —CONH 2 , —CONH(C 1 -C 6  alkyl), or —CON(C 1 -C 6  alkyl) 2 , wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and   Z 2  is —H, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), —NH 2 , —NH(C 1 -C 6  alkyl), or —N(C 1 -C 6  alkyl) 2 , wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         12 . The method of  claim 11 , wherein:
 Z 1  is —H, —F, —Cl, —CF 3 , —CH 3 , or —CN; and   Z 2  is —H or an optionally substituted C 1 -C 6  alkyl.   
     
     
         13 . The method of  claim 12 , wherein:
 R 2  is —H; and   R 3  is —H, —F, —Cl, —CF 3 , —CH 3 , —C 2 H 5 , —NH 2 , —NH(CH 3 ), or —N(CH 3 ) 2 .   
     
     
         14 . The method of  claim 13 , wherein:
 Z 1  is —H, —F, —Cl, —CF 3 , —CH 3 , or —CN;   Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   R 1  is —H;   R 2  is —H;   R 3  is independently —H, —Cl or —F;   R 6  and R 7  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring;   each R 8  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ;   each R 9  is independently —H or —CH 3 ;   R 11  and R 12  are each independently —H or —CH 3 ; and   R 13  and R 14  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring.   
     
     
         15 . The method of  claim 11 , wherein the compound is represented by any one of the structural formulae below (II), (III), (IV) and (V): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 3  is —H, —F, —Cl, —CF 3 , —NH 2 , —NH(CH 3 ), or —N(CH 3 ) 2 ; 
 Z 1  is —H, —F, —Cl, —CF 3 , C 1 -C 4  alkyl, —CH 2 NH 2 , —C(O)NH 2 , —C(O)NH(CH 3 ), —C(O)N(CH 3 ) 2 , —O(C 1 -C 4  alkyl), or —CN; 
 each R and R′ are independently —H or C 1 -C 6  alkyl; 
 ring A is an optionally substituted, C 4 -C 7  non-aromatic carbocycle; 
 rings B and C are each independently an optionally substituted, 4-7 membered non-aromatic heterocycle; 
 ring D is an optionally substituted, 4-7 membered non-aromatic heterocycle; 
 
     
     
         16 . The method of  claim 15 , wherein:
 Z 1  is —H, —F, —Cl, —CF 3 , —CH 3 , or —CN; and   Z 2  is —H or an optionally substituted C 1 -C 6  alkyl.   
     
     
         17 . The method of  claim 16 , wherein R 3  is independently —H, —Cl or —F. 
     
     
         18 . The method of  claim 17 , wherein:
 R 6  and R 7  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring;   each R 8  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 .   each R 9  is independently —H or —CH 3 ;   R 11  and R 12  are each independently —H or —CH 3 ; and   R 13  and R 14  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring.   
     
     
         19 . The method of  claim 18 , wherein the compound is represented by the following structural formula (XIA) or (XIB): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring A is a 5-7 membered ring optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 15 , wherein the compound is represented by the following structural formula (XIIA) or (XIIB): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; wherein:
 ring B is optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 15 , wherein the compound is represented by the following structural formula (XIII): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring C is 5-6 membered and optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6  alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         39 . The method of  claim 38 , wherein R 10  is —H or C 1 -C 6 -alkyl. 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 15 , wherein the compound is represented by the following structural formula (XIV): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring D is optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 6 , wherein R 4  is: 
       
         
           
           
               
               
           
         
       
       wherein:
 ring E is a C 4 -C 10  non-aromatic carbocycle optionally further substituted with one or more instances of J A ; 
 rings F is a 4-8 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; 
 R 9  is independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; 
 R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
 s is 0, 1 or 2; and 
 x is 0, 1 or 2. 
 
     
     
         47 . The method of  claim 46 , wherein ring F is selected from any one of rings F1-F6: 
       
         
           
           
               
               
           
         
         each of rings F1-F6 optionally and independently substituted; and 
         each R f  is independently —H or C 1 -C 6  alkyl optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy and C 2 -C 6  alkoxyalkoxy. 
       
     
     
         48 . The method of  claim 47 , wherein each rings F1-F6 are independently and optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 4  alkoxy, and C 1 -C 4  alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl). 
     
     
         49 . The method of  claim 48 , wherein:
 R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; and   ring E is a C 4 -C 8  non-aromatic carbocycle optionally further substituted with one or more instances of J A .   
     
     
         50 . (canceled) 
     
     
         51 . The method of  claim 6 , wherein R 4  is: 
       
         
           
           
               
               
           
         
         each of rings G1-G4 is independently a 5-10 membered non-aromatic bridged carbocycle optionally further substituted with one or more instances of J A , and ring G5 is a 5-10 membered non-aromatic bridged heterocycle optionally further substituted with one or more instances of J B ; 
         X is —O—, —S—, or —NR 9 —; 
         R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; 
         R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
         R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         R g  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         q is 0, 1 or 2; 
         x is 0, 1 or 2; and 
         r is 1 or 2. 
       
     
     
         52 . The method of  claim 51 , wherein R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         53 . The method of  claim 52 , wherein
 each of R 8  and R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C z —C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; and   R 21 , R 22 , R 23 , and R 24  are each independently —H, halogen, —OH, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy.   
     
     
         54 . (canceled) 
     
     
         55 . The method of  claim 53 , wherein:
 Q 2  is independently —O—, —CO 2 —, —OC(O)—, —C(O)NR—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —CO 2 SO 2 —, —P(O) 2 O—, or —(CR 6 R 7 ) p —Y 1 —.   
     
     
         56 . The method of  claim 55 , wherein Q 2  is independently —O— or —CO 2 —. 
     
     
         57 . (canceled) 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 55 , wherein:
 R 1  is —H;   R 2  is —H, —CH 3 , —CH 2 OH, or —NH 2 ;   R 3  is —H, —F, —Cl, C 1-4  alkyl, or C 1-4  haloalkyl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   R 5  is: i) —H; ii) an optionally substituted C 1 -C 6  alkyl group; iii) an optionally substituted, C 3 -C 7  non-aromatic carbocycle; iv) an optionally substituted, 4-7 membered non-aromatic heterocycle; v))an optionally substituted phenyl group; vi) an optionally substituted 5-6 membered heteroaryl ring; or optionally, together with R and the nitrogen atom to which it is attached, form a 5-7 membered, optionally substituted non-aromatic heterocycle; and   said alkyl group represented by R 5  is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(O—C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (O—C 4  alkyl), C 1 -C 4  alkoxy, —NRCO(C 1 -C 4  alkyl), —CONR(C 1 -C 4  alkyl), —NRCO 2 (C 1 -C 4  alkyl), a C 3 -C 7  non-aromatic carbocycle optionally substituted with one or more instances of J E1 , a 4-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; and a phenyl optionally substituted with one or more instances of J E1 ; and   wherein each of said carbocycle, heterocycle, phenyl and heteroary represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl) and —CO 2 H, wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         61 . (canceled) 
     
     
         62 . The method of  claim 55 , wherein:
 R 1  is —H;   R 2  is —H or —CH 2 OH;   R 3  is —H, —F, or —Cl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H;   Z 3  is —H;   R 5  is independently: i) —H or ii) a C 1 -C 6 -alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl), —CO 2 H, C 3 -C 8  non-aromatic carbocycle, 4-8 membered non-aromatic heterocycle, phenyl, and 5-6 membered heteroaryl;   wherein each of said alkyl groups referred to in the substituents of the C 1 -C 6 -alkyl group represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and   wherein each of said carbocycle, phenyl, heterocycle, and heteroaryl referred to in the substituents of the C 1 -C 6 -alkyl group represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         63 . (canceled) 
     
     
         64 . (canceled) 
     
     
         65 . The method of  claim 6 , wherein:
 R 4  is:   
       
         
           
           
               
               
           
         
         ring A is a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 8  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 9  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 11  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, wherein each of said carbocycle is independently and optionally substituted with one or more instances of J A  and wherein each carbocycle is independently and optionally substituted with one or more instances of J B ; 
         R 1  is —H; 
         R 2  is —H, —CH 3 , —CH 2 OH, or —NH 2 ; 
         R 3  is —H, —F, —Cl, C 1-4  alkyl, or C 1-4  haloalkyl; 
         Z 1  is —H, —F, or —Cl; 
         Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
         Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
         Q 2  is independently —O—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 7 ) p —Y 1 —; 
         Y 1  is —O—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—,—NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, or —CO 2 SO 2 —; 
         R 5  is: i) —H; ii) an optionally substituted C 1 -C 6  alkyl group; iii) an optionally substituted, C 3 -C 7  non-aromatic carbocycle; iv) an optionally substituted, 4-7 membered non-aromatic heterocycle; v))an optionally substituted phenyl group; vi) an optionally substituted 5-6 membered heteroaryl ring; or optionally, together with R and the nitrogen atom to which it is attached, form a 5-7 membered, optionally substituted non-aromatic heterocycle; and 
         said alkyl group represented by R 5  is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), C 1 -C 4  alkoxy, —NRCO(C 1 -C 4  alkyl), —CONR(C 1 -C 4  alkyl), —NRCO 2 (C 1 -C 4  alkyl), a C 3 -C 7  non-aromatic carbocycle optionally substituted with one or more instances of J E1 , a 4-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; and a phenyl optionally substituted with one or more instances of J E1 ; 
         wherein each of said carbocycle, heterocycle, phenyl and heteroary represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl) and —CO 2 H, wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; 
         each of R 8  and R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; 
         R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, and C 1 -C 6  alkoxy; and 
         each of J A  and J B  is independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and 
         n is 0 or 1; 
         x is 0 or 1. 
       
     
     
         66 . The method of  claim 65 , wherein:
 R 4  is:   
       
         
           
           
               
               
           
         
         each of rings G1-G4 is independently a 5-10 membered non-aromatic bridged carbocycle optionally further substituted with one or more instances of J A , and ring G5 is a 5-10 membered non-aromatic bridged heterocycle optionally further substituted with one or more instances of J B ; 
         X is —O—, —S—, or —NR—; 
         R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl); 
         R g  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C z —C 6  alkoxyalkoxy; and 
         q is 0, 1 or 2; and 
         r is 1 or 2. 
       
     
     
         67 . The method of  claim 66 , wherein:
 R 1  is —H;   R 2  is —H;   R 3  is —H, —F, or —Cl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H;   Z 3  is —H;   X is —O—;   R 5  is —H, an optionally substituted C 1 -C 6  alkyl, or optionally substituted phenyl;   each R 8  is independently —H, halogen, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, or —O(C 1 -C 4  alkyl);   each of R 9 , R 13 , and R 14  is independently —H or C 1 -C 4  alkyl;   R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkyl, and —O(C 1 -C 6  alkyl); and   each rings G1-G5 are independently and optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), C 1 -C 4  alkyl that is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and C 1 -C 4  alkoxy.   
     
     
         68 . (canceled) 
     
     
         69 . The method of  claim 1 , further comprising co-administering and additional therapeutic agent. 
     
     
         70 . The method of  claim 69 , wherein the additional therapeutic agent is selected from an antiviral agent or an Influenza vaccine, or both. 
     
     
         71 . A compound represented by structural formula (IA): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         Z 1  is —R*, —F, —Cl, —CN, —OR*, —CO 2 R*, —NO 2 , or —CON(R*) 2 ; 
         Z 2  is —R*, —OR*, —CO 2 R*, —NR* 2 , or —CON(R*) 2 ; 
         Z 3  is —H, —OH, halogen, —NH 2 ; —NH(C 1 -C 4  alkyl); —N(C 1 -C 4  alkyl) 2 , —O(C 1 -C 4  alkyl), or C 1 -C 6  alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
         R 1  is —H, C 1 -C 6  alkyl, —S(O) 2 —R, or —C(O)OR″; 
         R 2  is —H; —F; —NH 2 ; —NH(C 1 -C 4  alkyl); —N(C 1 -C 4  alkyl) 2 ; —C═N—OH; cyclopropyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, —OCH 3 , and —CH 3 ; or C 1 -C 4  alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); and 
         R 3  is —H, —Cl, —F, —Br, —OH, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —CN, or C 1 -C 4  aliphatic that is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; R 4  is: 
       
       
         
           
           
               
               
           
         
       
       wherein:
 ring A is a C 3 -C 10  non-aromatic carbocycle optionally further substituted with one or more instances of J A  or a 3-10 membered non-aromatic heterocycle optionally further substituted with one or more instances of J B ; 
 rings B and C are each independently a 4-10 membered, non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ; 
 ring D is a 4-10 membered, non-aromatic heterocycle optionally substituted with one or more instances of J B1 ; 
 ring A and R 8  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 9  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 11  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, wherein each carbocycle is optionally further substituted with one or more instances of J A , and wherein each heteroocycle is optionally further substituted with one or more instances of J B ; 
 each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, —NCO, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 4-8 membered ring that is optionally substituted with one or more instances of J E1 ; 
 Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 7 ) p —Y 1 —; 
 Q 2  is independently a bond, —O—, —S—, —NR—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, —NRSO 2 NR—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 7 ) p —Y 1 —; and 
 Q 3  is independently a bond, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —C(O)NR—, —SO 2 —, —SO 2 N(R)—, —C(O)NRC(O)O— or —(CR 6 R 7 ) p —Y 1 —; 
 each Y 1  is independently a bond, —O—, —S—, —NR—, —C(O)—, —C(═NR)—, —C(═NR)NR—, —NRC(═NR)NR—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, —NRSO 2 NR—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, or —CO 2 SO 2 —; 
 R 5  is: i) —H; ii) a C 1 -C 6  aliphatic group optionally substituted with one or more instances of J C1 ; iii) a C 3 -C 10  non-aromatic carbocycle, or a 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of J C1 ; or iv) a 4-10 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of J D1 ; or 
 R 5 , together with each of Q 1 , Q 2  and Q 3 , optionally and independently forms a 4-8 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; and 
 R 6  and R 7  are each independently —H or C 1 -C 6  alkyl optionally substituted with one or more substitutents selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy, or optionally R 6  and R 7 , together with the carbon atom to which they are attached, form a cyclopropane ring optionally substituted with one or more instances of methyl; 
 R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; or R 8 , together with Q 2  and R 5 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; or 
 R 10  is independently —H or a C 1 -C 6  alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, C 2 -C 6  alkoxyalkoxy, C 3 -C 8  non-aromatic carbocycle, phenyl, 4-8 membered non-aromatic heterocycle, and 5-6 membered heteroaryl group, wherein each of said carbocycle, phenyl, heterocycle and heteroaryl group is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14  together with the carbon atom to which they are attached form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
 R and R′ are each independently —H or C 1 -C 6  alkyl optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; or 
 optionally R′, together with R 5  and the nitrogen atom to which they are attached, forms a 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J p1 ; 
 R″ is independently: i) a C 1 -C 6 -alkyl optionally substituted with one or more substituents selected independently from the group consisting of halogen, cyano, hydroxyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; or ii) a C 3 -C 6  carbocyclic group, a 5-6 membered heteroaryl group, or a phenyl group, each optionally and independently being substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, nitro, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkoxyalkyl, C 1 -C 6 -aminoalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6 -hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 R* is independently: i) —H; ii) a C 1 -C 6  alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 3 -C 8  non-aromatic carbocycle, 5-6 membered non-aromatic heterocycle, phenyl, 5-6 membered heteroaryl, —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl); 
 wherein each of said alkyl groups in —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl) is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and 
 wherein each of said carbocycle, heterocycle, phenyl, and heteroaryl is independently and optionally substituted with one or more instances of J E1 ; or iii) a C 3 -C 8  non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is independently and optionally substituted with one or more instances of J E1 ; and 
 each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(═NR)R c , —C(═NR)NR b R c , —NRC(═NR)NR b R c , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , —NRSO 2 NR c R b , —P(O)(OR a ) 2 , —OP(O)(OR a ) 2 , —P(O) 2 (OR a ), and —CO 2 SO 2 R b , or optionally, two J C1  and two J D1 , respectively, together with the atom(s) to which they are attached, independently form a 4-8-membered ring that is optionally substituted with one or more instances of J E1 ; 
 each J E1  is independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), and —C(O)(C 1 -C 6 -alkyl), wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and 
 each R a  is independently: i) a C 1 -C 6  aliphatic group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, amido, —O(C 1 -C 6  alkyl), —C(O)(C 1 -C 6 -alkyl), C 3 -C 8  non-aromatic carbocycle, 4-8 membered non-aromatic heterocycle, 5-10 membered heteroaryl group, and 6-10 membered carbocyclic aryl group; wherein each of said alkyl groups for the substituents of the C 1 -C 6  aliphatic group represented by R a  is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and wherein each of said carbocycle, heterocycle, heteroaryl, and carbocyclic aryl groups for the substituents of the C 1 -C 6  aliphatic group represented by R a  is optionally and independently substituted with one or more instances of J E1 ; 
 
       ii) a C 3 -C 8  non-aromatic carbocycle, or a 4-8 membered non-aromatic heterocycle, each of which is optionally and independently substituted with one or more instances of J E1 ; 
       iii) a 5-10 membered heteroaryl, or 6-10 membered carbocyclic aryl group, each of which is optionally and independently substituted with one or more instances of J E1 ; and
 R b  and R c  are each independently R a  or —H; or optionally, R b  and R c , together with the nitrogen atom(s) to which they are attached, each independently form a 5-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; 
 p is independently 1, 2, 3 or 4; 
 n and m are each independently 0 or 1 when rings A and B are 3-6-membered; or n and m are each independently 0, 1 or 2 when rings A and B are 7-10-membered; and 
 k is 0, 1 or 2; 
 x and y are each independently 0, 1 or 2; 
 z is 1 or 2; and 
 provided that if Y 1  is a bond, then R 5  is neither —H nor a C 1 -C 6  aliphatic group; and 
 provided that if each Q 2  and Q 3  independently is a bond, then R 5  is neither —H nor a C 1 -C 6  aliphatic group. 
 
     
     
         72 . The compound of  claim 71 , represented by structural formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 2  is —H; —CH 3 , —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 ; 
 ring A is a C 3 -C 8  non-aromatic carbocycle or heterocycle, the carbocycle and heterocycle optionally further substituted with one or more instances of J A  and J B , respectively; 
 rings B and C are each independently a 4-8 membered, non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ; 
 ring D is a 4-8 membered, non-aromatic heterocycle optionally substituted with one or more instances of J D1 ; 
 Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —C(═NR)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, or —(CR 6 R 7 ) p —Y 1 —; 
 Q 2  is independently a bond, —O—, —S—, —NR—, —C(O)—, —C(═NR)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, —NRSO 2 NR—, or —(CR 6 R 2 ) p —Y 1 —; and 
 Q 3  is independently a bond, —C(O)—, —C(═NR)—, —CO 2 —, —C(O)NR—, —SO 2 —, —SO 2 N(R)—, —C(O)NRC(O)O— or —(CR 6 R 2 ) p —Y 1 —; 
 each of Q 2  and Q 3 , together with R 5 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; 
 each Y 1  is independently a bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, or —NRSO 2 NR—; 
 R 5  is: i) —H; ii) a C 1 -C 6  aliphatic group optionally substituted with one or more instances of J C1 ; iii) a C 3 -C 8  non-aromatic carbocycle, or a 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of J C1 ; or iv) a 4-8 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of J D1 ; or 
 R 5 , together with Q 2  and R 8 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; 
 R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; or R 8 , together with Q 2  and R 5 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ; and 
 R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14  together with the carbon atom to which they are attached form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
 each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , —NRSO 2 NR c R b , and —P(O) 2 (OR a ), or optionally, two J C1  and two J D1 , respectively, together with the atom(s) to which they are attached, independently form a 5-7-membered ring that is optionally substituted with one or more instances of J E1  and fused to the respective ring to which they are attached; and 
 n and m are each independently 0 or 1 when rings A and B are 3-6-membered; or n and m are each independently 0, 1 or 2 when rings A and B are 7-8-membered. 
 
     
     
         73 . The compound of  claim 72 , wherein:
 ring A is a C 3 -C 8  non-aromatic carbocycle optionally and independently further substituted with one or more instances of J A ;   rings B and C are each independently a 4-8 membered, non-aromatic heterocycle optionally and independently further substituted with one or more instances of J B ;   ring D is a 4-8 membered, non-aromatic heterocycle optionally substituted with one or more instances of J D1 ;   each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 5-7 membered ring that is optionally substituted with one or more instances of J E1  and fused to the ring to which they are attached; and   each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , and —NRSO 2 NR c R b , or optionally, two J C1  and two J D1 , respectively, together with the atoms to which they are attached, independently form a 5-7-membered ring that is optionally substituted with one or more instances of J E1 , and fused to the respective ring to which they are attached;   Q 1  is independently a bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, —NRSO 2 NR—, or —(CR 6 R 7 ) p —Y 1 —;   Q 2  is independently a bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, —NRSO 2 NR—, or —(CR 6 R 7 ) p —Y 1 —; and   Q 3  is independently a bond, —C(O)—, —CO 2 —, —C(O)NR—, —SO 2 —, —SO 2 N(R)—, —C(O)NRC(O)O— or —(CR 6 R 7 ) p —Y 1 —; or   each of Q 2  and Q 3 , together with R 5 , optionally and independently forms a 5-7 membered, non-aromatic ring optionally substituted with one or more instances of J E1 ;   each Y 1  is independently a bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 N(R)—, or —NRSO 2 NR—;   R 5  is: i) —H; ii) a C 1 -C 6  aliphatic group optionally substituted with one or more instances of J C1 ; iii) a C 3 -C 8  non-aromatic carbocycle, or 6-10 membered carbocyclic aryl group, each optionally and independently substituted with one or more instances of J C1 ; or iv) a 4-8 membered non-aromatic heterocycle, or a 5-10 membered heteroaryl group, each optionally and independently substituted with one or more instances of J p1 ; and   R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy.   
     
     
         74 . The compound of any one of  claims 71 - 73 , wherein R 1  is —H or C 1 -C 6  alkyl. 
     
     
         75 . The compound of  claim 74 , wherein R 1  is —H. 
     
     
         76 . The compound of  claim 75 , wherein R 2  is —H, —F, —CH 3 , —CH 2 OH, or —NH 2 . 
     
     
         77 . (canceled) 
     
     
         78 . The compound of  claim 76 , wherein R 3  is —H, —Cl, —F, —Br, —CN, —CF 3 , —O(C 1 -C 4  alkyl), —OH, —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 . 
     
     
         79 . The compound of  claim 73 , wherein the compound is represented by the following structural formula (VI): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         80 . The compound of  claim 79 , wherein:
 Z 1  is —H, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), —F, —Cl, —CN, —CO 2 H, —CO 2 (O—C 6  alkyl), —CONH 2 , —CONH(C 1 -C 6  alkyl), or —CON(C 1 -C 6  alkyl) 2 , wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —OCO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and   Z 2  is —H, C 1 -C 6  alkyl, —O(C 1 -C 6  alkyl), —NH 2 , —NH(C 1 -C 6  alkyl), or —N(C 1 -C 6  alkyl) 2 , wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         81 . (canceled) 
     
     
         82 . (canceled) 
     
     
         83 . The compound of  claim 79 , wherein:
 Z 1  is —H, —F, —Cl, —CF 3 , —CH 3 , or —CN;   Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   R 1  is —H;   R 2  is —H;   R 3  is independently —H, —Cl or —F;   R 6  and R 2  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring;   each R 8  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 .   each R 9  is independently —H or —CH 3 ;   R 11  and R 12  are each independently —H or —CH 3 ; and   R 13  and R 14  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring.   
     
     
         84 . The compound of  claim 80 , wherein the compound is represented by any one of structural formulae (II), (III), (IV) and (V): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 3  is —H, —F, —Cl, —CF 3 , —NH 2 , —NH(CH 3 ), or —N(CH 3 ) 2 ; 
 Z 1  is —H, —F, —Cl, —CF 3 , C 1 -C 4  alkyl, —CH 2 NH 2 , —C(O)NH 2 , —C(O)NH(CH 3 ), —C(O)N(CH 3 ) 2 , —O(C 1 -C 4  alkyl), or —CN; 
 each R and R′ are independently —H or C 1 -C 6  alkyl; 
 ring A is an optionally substituted, C 4 -C 7  non-aromatic carbocycle; 
 rings B and C are each independently an optionally substituted 4-7 membered non-aromatic heterocycle; 
 ring D is an optionally substituted 4-7 membered non-aromatic heterocycle; 
 each of J A  and J B  is independently selected from the group consisting of halogen, cyano, oxo, and Q 1 -R 5 ; or optionally two J A  and two J B , respectively, together with the atom(s) to which they are attached, independently form a 5-7 membered ring that is optionally substituted with one or more instances of J E1  and fused to the ring to which they are attached; 
 each of J C1  and J D1  is independently selected from the group consisting of halogen, cyano, oxo, R a , —OR b , —SR b , —S(O)R a , —SO 2 R a , —NR b R c , —C(O)R b , —C(O)OR b , —OC(O)R b , —NRC(O)R b , —C(O)NR b R c , —NRC(O)NR b R c , —NRC(O)OR b , —OCONR b R c , —C(O)NRCO 2 R b , —NRC(O)NRC(O)OR b , —C(O)NR(OR b ), —SO 2 NR c R b , —NRSO 2 R b , and —NRSO 2 NR c R b , or optionally, two J C1  and two J D1 , respectively, together with the atoms to which they are attached, independently form a 5-7-membered ring that is optionally substituted with one or more instances of J E1 , and fused to the respective ring to which they are attached; 
 Q 1  is independently a bond, —O—, —S—, —NR′—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —S(O)—, —SO 2 —, —SO 2 NR′—, —NRSO 2 —, or —NRSO 2 NR′—, or —(CR 6 R 7 ) p —Y 1 —; 
 Q 2  is independently bond, —O—, —S—, —NR—, —C(O)—, —CO 2 —, —OC(O)—, —C(O)NR—, —C(O)NRC(O)O—, —NRC(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —S(O)—, —SO 2 —, —N(R)SO 2 —, —SO 2 NR′—, —NRSO 2 NR′—, or —(CR 6 R 7 ) p —Y 1 —; and 
 Q 3  is independently a bond, —C(O)—, —CO 2 —, —C(O)NR′—, —SO 2 —, —SO 2 NR′—, —C(O)NRC(O)O—, or —(CR 6 R 7 ) p —Y 1 —; 
 provided that if Q 2 -R 5  is —OR 5  or —NR′R 5 , then ring A is further substituted with one or more instances of J A  other than —H; and 
 provided that if Q 3  is —C(O)—, then R 5  is a substituted C 1 -C 6  aliphatic group; an optionally substituted C 3 -C 8  non-aromatic carbocycle; an optionally substituted, 6-10-membered carbocyclic aryl group; an optionally substituted, 4-8 membered non-aromatic heterocycle; or an optionally substituted 5-10 membered heteroaryl group. 
 
     
     
         85 . The compound of  claim 84 , wherein:
 Z 1  is —H, —F, —Cl, —CF 3 , —CH 3 , or —CN; and   Z 2  is —H or an optionally substituted C 1 -C 6  alkyl.   
     
     
         86 . The compound of  claim 85 , wherein R 3  is —H, —Cl or —F. 
     
     
         87 . The compound of  claim 86 , wherein:
 R 6  and R 7  are each independently —H or —CH 3 , or together with the carbon atoms to which they are attached they form a cyclopropane ring;   each R 8  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 .   each R 9  is independently —H or —CH 3 ;   R 11  and R 12  are each independently —H or —CH 3 ; and   R 13  and R 14  are each independently —H or —CH 3 , or optionally R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring.   
     
     
         88 . The compound of  claim 87 , wherein the compound is represented by structural formula (XIA) or (XIB): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring A is a 5-7 membered non-aromatic carbocycle optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         89 . (canceled) 
     
     
         90 . (canceled) 
     
     
         91 . (canceled) 
     
     
         92 . (canceled) 
     
     
         93 . (canceled) 
     
     
         94 . (canceled) 
     
     
         95 . (canceled) 
     
     
         96 . (canceled) 
     
     
         97 . (canceled) 
     
     
         98 . (canceled) 
     
     
         99 . (canceled) 
     
     
         100 . The compound of  claim 87 , wherein the compound is represented by structural formula (XIIA) or (XIIB): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; wherein:
 ring B is optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         101 . (canceled) 
     
     
         102 . (canceled) 
     
     
         103 . (canceled) 
     
     
         104 . (canceled) 
     
     
         105 . (canceled) 
     
     
         106 . (canceled) 
     
     
         107 . (canceled) 
     
     
         108 . (canceled) 
     
     
         109 . The compound of  claim 87 , wherein the compound is represented by structural formula (XIII): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring C is a 5-6 membered non-aromatic heterocycle optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         110 . The compound of  claim 109 , wherein R 10  is —H or C 1 -C 6 -alkyl. 
     
     
         111 . (canceled) 
     
     
         112 . (canceled) 
     
     
         113 . (canceled) 
     
     
         114 . The compound of  claim 87 , wherein the compound is represented by the following structural formula (XIV): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 ring D is optionally further substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl and alkenyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy. 
 
     
     
         115 . (canceled) 
     
     
         116 . (canceled) 
     
     
         117 . The compound of  claim 83 , wherein R 4  is: 
       
         
           
           
               
               
           
         
       
       wherein:
 ring E is a C 4 -C 10  non-aromatic carbocycle optionally further substituted with one or more instances of J A ; 
 rings F is a 4-8 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; 
 R 9  is independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 2 -C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; 
 R 11 , R 12 , R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
 optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
 s is 0, 1 or 2; and 
 x is 0, 1 or 2. 
 
     
     
         118 . The compound of  claim 117 , wherein ring F is selected from any one of rings F1-F6: 
       
         
           
           
               
               
           
         
         each of rings F1-F6 optionally and independently substituted; and 
         each R f  is independently —H or C 1 -C 6  alkyl optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy and C 2 -C 6  alkoxyalkoxy. 
       
     
     
         119 . The compound of  claim 118 , wherein each rings F1-F6 are independently and optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 4  alkoxy, and C 1 -C 4  alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl). 
     
     
         120 . The compound of  claim 118 , wherein:
 R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; and   ring E is a C 4 -C 8  non-aromatic carbocycle optionally further substituted with one or more instances of J A .   
     
     
         121 . (canceled) 
     
     
         122 . The compound of  claim 83 , wherein R 4  is: 
       
         
           
           
               
               
           
         
         each of rings G1-G4 is independently a 5-10 membered non-aromatic bridged carbocycle optionally further substituted with one or more instances of J A , and ring G5 is a 5-10 membered non-aromatic bridged heterocycle optionally further substituted with one or more instances of J B ; 
         X is —O—, —S—, or —NR—; 
         R 8  and R 9  are each independently —H, halogen, cyano, hydroxy, amino, carboxy, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C z —C 6  alkoxyalkyl, C 1 -C 6  aminoalkyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  carboxyalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, or C 2 -C 6  alkoxyalkoxy; 
         R 13  and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         optionally, R 13  and R 14 , together with the carbon atom to which they are attached, form a cyclopropane ring, optionally substituted with one or more instances of methyl; 
         R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         R g  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; 
         q is 0, 1 or 2; 
         x is 0, 1 or 2; and 
         r is 1 or 2. 
       
     
     
         123 . The compound of  claim 122 , wherein R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         124 . The compound of  claim 123 , wherein:
 each of R 8  and R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C z —C 4  alkoxyalkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; and   R 21 , R 22 , R 23 , and R 24  are each independently —H, halogen, —OH, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy.   
     
     
         125 . (canceled) 
     
     
         126 . The compound of  claim 124 , wherein:
 Q 2  is independently —O—, —CO 2 —, —OC(O)—, —C(O)NR—, —NRC(O)—, —NRC(O)NR—, —NRCO 2 —, —OC(O)NR—, —CO 2 SO 2 —, —P(O) 2 O—, or —(CR 6 R 2 ) p —Y 1 —.   
     
     
         127 . The compound of  claim 126 , wherein Q 2  is independently —O— or —CO 2 —. 
     
     
         128 . (canceled) 
     
     
         129 . (canceled) 
     
     
         130 . (canceled) 
     
     
         131 . The compound of  claim 126 , wherein:
 R 1  is —H;   R 2  is —H, —CH 3 , —CH 2 OH, or —NH 2 ;   R 3  is —H, —F, —Cl, C 1-4  alkyl, or C 1-4  haloalkyl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl);   R 5  is: i) —H; ii) an optionally substituted C 1 -C 6  alkyl group; iii) an optionally substituted, C 3 -C 2  non-aromatic carbocycle; or iv) an optionally substituted, 4-7 membered non-aromatic heterocycle; or optionally, together with R and the nitrogen atom to which it is attached, form a 5-7 membered, optionally substituted non-aromatic heterocycle; and   said alkyl group represented by R 5  is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), C 1 -C 4  alkoxy, a C 3 -C 7  non-aromatic carbocycle optionally substituted with one or more instances of J E1 , a 4-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; and a phenyl optionally substituted with one or more instances of J E1 ; and   wherein each of said carbocycles and heterocycles represented by R 5 , and referred to for the substituents of the C 1 -C 6  alkyl group represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl) and —CO 2 H, wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         132 . (canceled) 
     
     
         133 . The compound of  claim 126 , wherein:
 R 1  is —H;   R 2  is —H or —CH 2 OH;   R 3  is —H, —F, or —Cl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H;   Z 3  is —H;   R 5  is independently: i) —H or ii) a C 1 -C 6 -alkyl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl), —CO 2 H, C 3 -C 8  non-aromatic carbocycle, 4-8 membered non-aromatic heterocycle, phenyl, and 5-6 membered heteroaryl;   wherein each of said alkyl groups referred to in the substituents of the C 1 -C 6 -alkyl group represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and   wherein each of said carbocycle, phenyl, heterocycle, and heteroaryl referred to in the substituents of the C 1 -C 6 -alkyl group represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy.   
     
     
         134 . (canceled) 
     
     
         135 . (canceled) 
     
     
         136 . The compound of  claim 71 , wherein:
 R 4  is:   
       
         
           
           
               
               
           
         
         ring A is a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 8  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 9  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, or ring A and R 11  optionally form a non-aromatic, 5-10 membered, bridged carbocycle or heterocycle, wherein each of said carbocycle is independently and optionally substituted with one or more instances of J A  and wherein each carbocycle is independently and optionally substituted with one or more instances of J B ; 
         R 1  is —H; 
         R 2  is —H, —CH 3 , —CH 2 OH, or —NH 2 ; 
         R 3  is —H, —F, —Cl, C 1-4  alkyl, or C 1-4  haloalkyl; 
         Z 1  is —H, —F, or —Cl; 
         Z 2  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
         Z 3  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, and —O(C 1 -C 4  alkyl); 
         Q 2  is independently —O—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—, —NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, —CO 2 SO 2 —, or —(CR 6 R 7 ) p —Y 1 —; 
         Y 1  is —O—, —CO 2 —, —OC(O)—, —C(O)NR′—, —C(O)NRC(O)O—,—NRC(O)—, —NRC(O)NR′—, —NRCO 2 —, —OC(O)NR′—, —P(O)(OR)O—, —OP(O)(OR a )O—, —P(O) 2 O—, or —CO 2 SO 2 —; 
         R 5  is: i) —H; ii) an optionally substituted C 1 -C 6  alkyl group; iii) an optionally substituted, C 3 -C 7  non-aromatic carbocycle; iv) an optionally substituted, 4-7 membered non-aromatic heterocycle; v))an optionally substituted phenyl group; vi) an optionally substituted 5-6 membered heteroaryl ring; or optionally, together with R and the nitrogen atom to which it is attached, form a 5-7 membered, optionally substituted non-aromatic heterocycle; and 
         said alkyl group represented by R 5  is optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), C 1 -C 4  alkoxy, —NRCO(C 1 -C 4  alkyl), —CONR(C 1 -C 4  alkyl), —NRCO 2 (C 1 -C 4  alkyl), a C 3 -C 7  non-aromatic carbocycle optionally substituted with one or more instances of J E1 , a 4-7 membered non-aromatic heterocycle optionally substituted with one or more instances of J E1 ; and a phenyl optionally substituted with one or more instances of J E1 ; 
         wherein each of said carbocycle, heterocycle, phenyl and heteroary represented by R 5  is independently and optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, C 1 -C 4  alkyl, —O(C 1 -C 4  alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —C(O)(C 1 -C 4  alkyl), —OC(O)(C 1 -C 4  alkyl), —C(O)O(C 1 -C 4  alkyl) and —CO 2 H, wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; 
         each of R 8  and R 9  is independently —H, halogen, cyano, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, —O(C 1 -C 4 alkyl), —NH 2 , —NH(C 1 -C 4  alkyl), or —N(C 1 -C 4  alkyl) 2 ; 
         R 11 , R 12 , R 13 , and R 14  are each independently —H, halogen, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, and C 1 -C 6  alkoxy; and 
         each of J A  and J B  is independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl), and —CO 2 R b ; wherein each of said alkyl groups is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, oxo, —NH 2 , —NH(C 1 -C 4  alkyl), —N(C 1 -C 4  alkyl) 2 , —OCO(C 1 -C 4  alkyl), —CO(C 1 -C 4  alkyl), —CO 2 H, —CO 2 (C 1 -C 4  alkyl), and C 1 -C 4  alkoxy; and 
         n is 0 or 1; 
         x is 0 or 1. 
       
     
     
         137 . The compound of  claim 136 , wherein:
 R 4  is:   
       
         
           
           
               
               
           
         
         each of rings G1-G4 is independently a 5-10 membered non-aromatic bridged carbocycle optionally further substituted with one or more instances of J A , and ring G5 is a 5-10 membered non-aromatic bridged heterocycle optionally further substituted with one or more instances of J B ; 
         X is —O—, —S—, or —NR 9 —; 
         R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, hydroxy, C 1 -C 6  alkyl, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6  alkyl), —C(O)N(C 1 -C 6  alkyl) 2 , —C(O)(C 1 -C 6 -alkyl), —OC(O)(C 1 -C 6  alkyl), —NHC(O)(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl)C(O)(C 1 -C 6  alkyl); 
         R g  is —H or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, oxo, hydroxy, oxo, amino, carboxy, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, C 1 -C 6  aminoalkoxy, C 1 -C 6  cyanoalkoxy, C 1 -C 6  hydroxyalkoxy, and C 2 -C 6  alkoxyalkoxy; and 
         q is 0, 1 or 2; and 
         r is 1 or 2. 
       
     
     
         138 . The compound of  claim 137 , wherein:
 R 1  is —H;   R 2  is —H;   R 3  is —H, —F, or —Cl;   Z 1  is —H, —F, or —Cl;   Z 2  is —H;   Z 3  is —H;   X is —O—;   R 5  is —H, an optionally substituted C 1 -C 6  alkyl, or optionally substituted phenyl;   each R 8  is independently —H, halogen, hydroxy, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, C 2 -C 4  alkoxyalkyl, or —O(C 1 -C 4 alkyl);   each of R 9 , R 13 , and R 14  is independently —H or C 1 -C 4  alkyl;   R 21 , R 22 , R 23 , R 24 , and R 25  are each independently —H, halogen, —OH, C 1 -C 6  alkoxy, or C 1 -C 6  alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C 1 -C 6  alkyl, and —O(C 1 -C 6  alkyl); and   each rings G1-G5 are independently and optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, —NH 2 , —NH(C 1 -C 6  alkyl), —N(C 1 -C 6  alkyl) 2 , —O(C 1 -C 6  alkyl), C 1 -C 4  alkyl that is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, and C 1 -C 4  alkoxy.   
     
     
         139 . (canceled) 
     
     
         140 . (canceled) 
     
     
         141 . (canceled) 
     
     
         142 . (canceled) 
     
     
         143 . The compound of  claim 71 , wherein the compound is selected from any of the structures depicted in  FIG. 3 ,  FIG. 4 ,  FIG. 5 , and  FIG. 6 , or a pharmaceutically acceptable salt thereof. 
     
     
         144 . A compound selected from any of the structures depicted in  FIG. 7  or a pharmaceutically acceptable salt thereof. 
     
     
         145 . A pharmaceutical composition, comprising an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt of the same, and a pharmaceutically acceptable carrier, adjuvant or vehicle. 
     
     
         146 . (canceled) 
     
     
         147 . The method of  claim 1 , wherein t is 0 or 1; and j is 0 or 1. 
     
     
         148 . (canceled) 
     
     
         149 . (canceled) 
     
     
         150 . (canceled) 
     
     
         151 . The method of  claim 1 , wherein the compound is selected from the compounds depicted in  FIG. 3 ,  FIG. 4 ,  FIG. 5 ,  FIG. 6 ,  FIG. 7 , and  FIG. 8 , or a pharmaceutically acceptable salt thereof. 
     
     
         152 . A method of reducing the amount of influenza viruses in a biological sample or in a patient, comprising administering to said biological sample or patient an effective amount of a compound as described in  claim 1 , or a combination of said compounds thereof. 
     
     
         153 . A method of treating influenza in a patient, comprising administering to said patient an effective amount of a compound as described in  claim 1 , or a combination of said compounds thereof. 
     
     
         154 . A method preparing a compound represented by Structural Formula (IA): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, comprising the step of: 
       i) reacting compound A: 
       
         
           
           
               
               
           
         
       
       with compound B: 
       
         
           
           
               
               
           
         
       
       to form a compound represented by Structural Formula (XX): 
       
         
           
           
               
               
           
         
       
       and 
       ii) optionally deprotecting the Ts group of the compound of Structural Formula (XX) to form the compound of Structural Formula (IA),wherein:
 the variables of Structural Formulae (IA) and (XX), and compounds (A) and (B) are independently as defined in  claim 71 ; and 
 Ts is tosyl. 
 
     
     
         155 . A method preparing a compound represented by Structural Formula (IA): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, comprising the step of: 
       i) reacting compound C1 or C2: 
       
         
           
           
               
               
           
         
       
       with NH 2 R 4  to form a compound represented by Structural Formula (XX): 
       
         
           
           
               
               
           
         
       
       and 
       ii) optionally deprotecting the Ts group of the compound of Structural Formula (XX) to form the compound of Structural Formula (IA),wherein:
 the variables of Structural Formulae (IA) and (XX), and compounds (C1) and (C2) are independently as defined in  claim 71 ; and 
 Ts is tosyl. 
 
     
     
         156 . (canceled)