Antibacterial agents

Abstract

Antibacterial compounds of formula I are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

What is claimed is:  
     
         1 . A compound according to the formula I:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof,  
       wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (4) substituted or unsubstituted C 2 -C 6 -alkynyl,  
 (5) substituted or unsubstituted aryl,  
 (6) substituted or unsubstituted heterocyclyl, and  
 (7) substituted or unsubstituted heteroaryl;  
 
 L is absent or selected from the group consisting of 
 (1) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (2) —(NH) 0-1 —C(CH 2 ) j —NR 3L —(CH 2 ) k —,  
 (3) —(NH) 0-1 —C(R 1L , R 2L )—NR 3L —C(R 1L , R 2L )—,  
 (4) —C(R 1L , R 2L )—O—(R 1L , R 2L )—,  
 (5) —(CH 2 ) j —NR 3L —C(R 1L , R 2L )—CONH—(CH 2 ) k —,  
 (6) —CO—C(R 1L , R 2L )—NHCO—,  
 (7) —CONH—,  
 (8) —NHCO—,  
 wherein  
 R 1L , R 2L , and R 3L  are independently selected from the group consisting of 
 (a) H,  
 (b) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) C 1 -C 6 -alkyl substituted with aryl,  
 (d) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (e) C 1 -C 6 -alkyl substituted with heteroaryl,  
 
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S,  
 j is an integer of 0-4;  
 k is an integer of 0-4;  
 
 D is absent or selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl,  
 (2) substituted or unsubstituted aryl,  
 (3) substituted or unsubstituted heterocyclyl, and  
 (4) substituted or unsubstituted heteroaryl;  
 
 G is absent or selected from the group consisting of 
 (1) —(CH 2 ) i —O—(CH 2 ) i —,  
 (2) —(CH 2 ) i —S—(CH 2 ) i —,  
 (3) —(CH 2 ) i —NR g —(CH 2 ) i —,  
 (4) —C(═O)—,  
 (5) —NHC(═O)—,  
 (6) —C(═O)NH—,  
 (7) —(CH 2 ) i NHCH 2 C(═O)NH—,  
 (8) —C≡C—,  
 (9) —C≡C—C≡C—, and  
 (10) —C═C—;  
 wherein  
 R g  is H or substituted or unsubstituted C 1 -C 6 -alkyl;  
 i is an interger of 0-4;  
 
 Y is selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl,  
 (2) substituted or unsubstituted aryl,  
 (3) substituted or unsubstituted heterocyclyl, and  
 (4) substituted or unsubstituted heteroaryl;  
 
 X is selected from the group consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—,  
 (3) —C 2 -C 6 -alkenyl-C═O)—,  
 (4) —C 2 -C 6 -alkynyl-C═O)—, and  
 (5) —CH 2 —;  
 or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 B is a absent or  
                     wherein R 1b  and R 2b , are independently selected from the group consisting of 
 (a) H,  
 (b) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (d) substituted or unsubstituted C 2 -C 6 -alkynyl,  
 (e) substituted or unsubstituted aryl,  
 (f) substituted or unsubstituted heterocyclyl,  
 (g) substituted or unsubstituted heteroaryl,  
 (h) C 1 -C 6 -alkyl substituted with aryl,  
 (i) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (j) C 1 -C 6 -alkyl substituted with heteroaryl,  
   or R 1b  and R 2b , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;    q is an integer of 0-4;    
 R 3  is H or substituted or unsubstituted C 1 -C 6 -alkyl, 
 or R 3  and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;  
 
 R 4  is H or substituted or unsubstituted C 1 -C 6 -alkyl, 
 or R 4  and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 n is an integer of 0-2;  
 A is selected from the group consisting of 
 (1) H,  
 (2) —(CH 2 ) r C(R 1a , R 2a )(CH 2 ) s OR 3a ,  
 (3) —(CH 2 ) r C(R 1a , R 2a )N(R 4a , R 5a ),  
 (4) —(CH 2 ) r C(R 1a , R 2a )N(R 4a )COR 3a ,  
 (5) —(CH 2 ) r C(R 1a , R 2a )NHCON(R 4a , R 5a ),  
 (6) —(CH 2 ) r C(R 1a , R 2a )NHC(═NH)N(R 4a , R 5a ),  
 (7) —CH(R 1a , R 2a ),  
 (8) —C≡CH,  
 (9) —(CH 2 ) r C(R 1a , R 2a )CN,  
 (10) —(CH 2 ) r C(R 1a , R 2a )CO 2 R 3a , and  
 (11) —(CH 2 ) r C(R 1a , R 2a )CN(R 4a , R 5a ),  
 wherein R 1a , R 2a , R 3a , R 4a , and R 5a  are independently selected from the group consisting of 
 (a) H,  
 (b) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) substituted or unsubstituted aryl,  
 (d) substituted or unsubstituted heterocyclyl,  
 (e) substituted or unsubstituted heteroaryl,  
 (f) C 1 -C 6 -alkyl substituted with aryl,  
 (g) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (h) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 4a  and R 5a  together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 r is an integer of 0-4;  
 s is an integer of 0-4;  
 
 Q is absent or selected from the group consisting of 
 (1) —C(═O)N(R 1 , R 2 ),  
 (2) —NHC(═O)N(R 1 , R 2 ),  
 (3) —N(OH)C(═O)N(R 1 , R 2 ),  
 (4) —CH(OH)C(═O)N(R 1 , R 2 ),  
 (5) —CH[N(R 2q , R 3q )]C(═O)N(R 1 , R 2 ),  
 (6) —CHR 1q C(═O)N(R 1 , R 2 ),  
 (7) —CO 2 H,  
 (8) —C(═O)NHSO 2 R 4q ,  
 (9) —SO 2 NH 2 ,  
 (10) —N(OH)C(═O)R 1q ,  
 (11) —N(OH)SO 2 R 4q ,  
 (12) —NHSO 2 R 4q ,  
 (13) —SH,  
 (14) —CH(SH)(CH 2 ) 0-1 C(═O)N(R 1 , R 2 ),  
 (15) —CH(SH)(CH 2 ) 0-1 CO 2 H,  
 (16) —CH(OH)(CH 2 ) 0-1 CO 2 H,  
 (17) —CH(SH)CH 2 CO 2 R 1q ,  
 (18) —CH(OH)(CH 2 )SO 2 NH 2 ,  
 (19) —CH(CH 2 SH)NHCOR 1q ,  
 (20) —CH(CH 2 SH)NHSO 2 R 4q ,  
 (21) —CH(CH 2 SR 5q )CO 2 H,  
 (22) —CH(CH 2 SH)NHSO 2 NH 2 ,  
 (23) —CH(CH 2 OH)CO 2 H,  
 (24) —CH(CH 2 OH)NHSO 2 NH 2 ,  
 (25) —C(═O)CH 2 CO 2 H,  
 (26) —C(═O)(CH 2 ) 0-1 CONH 2 ,  
 (27) —OSO 2 NHR 5q ,  
 (28) —SO 2 NNNH 2 ,  
 (29) —P(═O)(OH) 2 ,  
                     
 (30)  
 (31)  
 (32)  
 
 R 1  is selected from the group consisting of 
 (1) —H,  
 (2) —OH,  
 (3) —OC 1-6 -alkyl,  
 (4) —N(R 2q , R 3q ), and  
 (5) substituted or unsubstituted C 1-6 -alkyl;  
 
 R 2  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (4) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (5) substituted or unsubstituted aryl,  
 (6) substituted or unsubstituted heterocyclyl,  
 (7) substituted or unsubstituted heteroaryl,  
 (8) C 1 -C 6 -alkyl substituted with aryl,  
 (9) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (10) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1  and R 2 , together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,  
 R 1q , R 2q , R 3q , R 4q , and R 5q  are selected from H or C 1 -C 6  alkyl,  
 
 wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.  
 
     
     
         2 . A compound of  claim 1 , wherein 
 wherein    E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl;  
   L is absent or selected from the group consisting of 
 (1) —(CH 2 ) j —NR 3L —(CH 2 ) k —,  
 (2) —C(R 1L , R 2L ) j —NR 3L —C(R 1L , R 2L ) k —,  
 (3) —C(R 1L , R 2L ) j —O—C(R 1L , R 2L ) k —,  
 (4) —(CH 2 ) j —NR 3L —C(R 1L , R 2L ) k —CONH—(CH 2 ) k —,  
 (5) —CO—C(R 1L , R 2L )—NHCO—,  
 (6) —CONH—, and  
 (7) —NHCO—,  
 wherein  
 R 1L, R   2L , R 3L  are independently selected from the group consisting of 
 (a) H,  
 (b) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) C 1 -C 6 -alkyl substituted with aryl,  
 (d) C 1 -C 6 -alkyl substituted with heterocyclyl,  
 (e) C 1 -C 6 -alkyl substituted with heteroaryl,  
 
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 j is an integer of 0-4;  
 k is an integer of 0-4;  
   D is absent or selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl,  
 (2) substituted or unsubstituted aryl,  
 (3) substituted or unsubstituted heterocyclyl,  
 (4) substituted or unsubstituted heteroaryl, and  
   G is absent or selected from the group consisting of 
 (1) —C(═O)—,  
 (2) —NHC(═O)—,  
 (3) —C(═O)NH—,  
 (4) —(CH 2 ) i NHCH 2 C(═O)NH—,  
 (5) —C≡C—, and  
 (6) —C≡C—C≡C—,  
 wherein i is an interger of 0-4;  
   Y is selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl,  
 (2) substituted or unsubstituted aryl,  
 (3) substituted or unsubstituted heterocyclyl, and  
 (4) substituted or unsubstituted heteroaryl;  
   X is selected from the group consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—,  
 (3) —C 2 -C 6 -alkenyl-(C═O)—,  
 (4) —C 2 -C 6 -alkynyl-(C═O)—, and  
 (5) —CH 2 —;  
 or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
   B is absent or                        wherein R 1b  and R 2b  are independently selected from the group consisting of 
 (a) H  
 (b)) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (d) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (e) substituted or unsubstituted aryl,  
 (f) substituted or unsubstituted heterocyclyl,  
 (g) substituted or unsubstituted heteroaryl,  
 (h) C 1 -C 6 -alkyl substituted with aryl,  
 (i) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (j) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1b  and R 2b , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
   q is an integer of 0-2;      R 3  is H or substituted or-unsubstituted C 1 -C 6 -alkyl, 
 or R 3  and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;  
   R 4  is H or substituted or unsubstituted C 1 -C 6 -alkyl, 
 or R 4  and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
   A is selected from the group consisting of 
 (1) H,  
 (2) —(CH 2 ) r C(R 1a , R 2a )(CH 2 ) s OR 3a ,  
 (3) —(CH 2 ) r C(R 1a , R 2a )N(R 4a , R 5a ),  
 (4) —(CH 2 ) r C(R 1a , R 2a )N(R 4a )COR 3a ,  
 (5) —(CH 2 ) r C(R 1a , R 2a )NHCON(R 4a , R 5a ),  
 (6) —(CH 2 ) r C(R 1a , R 2a )NHC(═NH)N(R 4a , R 5a ),  
 (7) —CH(R 1a , R 2a ),  
 (8) —C≡CH,  
 (9) —(CH 2 ) r C(R 1a , R 2a )CN, and  
 (10) —(CH 2 ) r C(R 1a , R 2a )CO 2 R 3a ,  
 wherein R 1a , R 2a , R 2a , R 4a , and R 5a , are independently selected from the group consisting of 
 (a) H,  
 (b) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (c) C 1 -C 6 -alkyl substituted with aryl,  
 (d) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (e) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 4a  and R 5a , together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 r is an integer of 0-4;  
   Q is absent or selected from the group consisting of 
 (1) —C(═O)N(R 1 , R 2 ),  
 (2) —NHC(═O)N(R 1 , R 2 ),  
 (3) —N(OH)C(═O)N(R 1 , R 2 ),  
 (4) —CH(OH)C(═O)N(R 1 , R 2 ),  
 (5) —CH[N(R 2q , R 3q )]C(═O)N(R 1 , R 2 ), and  
 (6) —CHR 1q C(═O)N(R 1 , R 2 ),  
   R 1  is selected from the group consisting of 
 (1) H,  
 (2) OH,  
 (3) OC 1-6 -alkyl,  
 (4) N(R 2q , R 3q ), and  
 (5) substituted or unsubstituted C 1-6 -alkyl;  
   R 2  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl,  
 (5) substituted or unsubstituted heteroaryl,  
 (6) C 1 -C 6 -alkyl substituted with aryl,  
 (7) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (8) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1  and R 2 , together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,  
 R 1q , R 2q , and R 3q  are selected from H or C 1 -C 6  alkyl,  
   wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.    
     
     
         3 . A compound of  claim 1 , having the formula II:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 X is selected from the group consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—, and  
 (2) —C 2 -C 6 -alkenyl-(C═O)—.  
 
 
     
     
         4 . A compound of claim I, having the formular III:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 X is selected from the groups consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—, and  
 (3) —C 2 -C 6 -alkenyl-(C═O)—.  
 
 
     
     
         5 . A compound of  claim 1 , having the formula IV:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 X is selected from the groups consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—, and  
 (3) —C 2 -C 6 -alkenyl-(C═O)—.  
 
 
     
     
         6 . A compound of  claim 1 , having the formula V:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 X is selected from the group consisting of 
 (1) —(C═O)—,  
 (2) —C 1 -C 6 -alkyl-(C═O)—, and  
 (3) —C 2 -C 6 -alkenyl-(C═O)—.  
 
 
     
     
         7 . A compound of  claim 1 , having the formula VI:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl,  
 or E and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,  
 
 R 1L , R 3L  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         8 . A compound of  claim 1 , having the formula VII:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl,  
 or E and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 R 1L , R 3L  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         9 . A compound of  claim 1 , having the formula VIII:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl,  
 or E and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 R 1L , R 3L  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         10 . A compound of  claim 1 , having the formula IX:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -allkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl,  
 or E and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 R 1L , R 3L  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         11 . A compound of  claim 1 , having the formula X:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 E is absent or selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl, and  
 (5) substituted or unsubstituted heteroaryl,  
 or E and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;  
 
 R 1L , R 3L  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1L  and R 3L , together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         12 . A compound of  claim 1 , having the formula XI:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 Y—X taken together, is selected from the group consisting of  
                                       
 
     
     
         13 . A compound of  claim 1 , having the formula XII:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 R 1b  and R 2b  are independently selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (4) substituted or unsubstituted C 2 -C 6 -alkenyl,  
 (5) substituted or unsubstituted aryl,  
 (6) substituted or unsubstituted heterocyclyl,  
 (7) substituted or unsubstituted heteroaryl,  
 (8) C 1 -C 6 -alkyl substituted with aryl,  
 (9) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (10) C 1 -C 6 -alkyl substituted with heteroaryl;  
 
 q is an integer of 0-2;  
 
     
     
         14 . A compound of  claim 1 , having the formula XIII:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 R 4  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl;  
 
 A is H or —CH(CH 3 )OH—;  
 R 1  is H or substituted or unsubstituted C 1-6 -alkyl;  
 R 2  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) substituted or unsubstituted aryl,  
 (4) substituted or unsubstituted heterocyclyl,  
 (5) substituted or unsubstituted heteroaryl,  
 (6) C 1 -C 6 -alkyl substituted with aryl,  
 (7) C 1 -C 6 -alkyl substituted with heterocyclyl,  
 (8) C 1 -C 6 -alkyl substituted with heteroaryl,  
 or R 1  and R 2  together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.  
 
 
     
     
         15 . A compound of  claim 1 , having the formula XIV:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 R 4  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl.  
 
 
     
     
         16 . A compound of  claim 1 , having the formula XV:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 
     
     
         17 . A compound of  claim 1 , having the formula XVI:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2 , —NHSO 2 CH 3 , and —NHCOCH 3 ;  
 
 R 4  is selected from the group consisting of 
 (1) H,  
 (2) substituted or unsubstituted C 1 -C 6 -alkyl,  
 (3) C 1 -C 6 -alkyl substituted with aryl,  
 (4) C 1 -C 6 -alkyl substituted with heterocyclyl, and  
 (5) C 1 -C 6 -alkyl substituted with heteroaryl;  
 
 
     
     
         18 . A compound of  claim 1 , having the formula XVII:  
       
         
           
           
               
               
           
         
       
       or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein 
 D-G-Y taken together, is selected from the group consisting of  
                                                                                             
 wherein 
 R is selected from the group consisting of —CH 3 , —C 2 H 5 , —CH 2 OH, —OH, —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —NO 2 , —CO 2 H, —CO 2 CH 3 , —CONH 2 , —NH 2 , —F, —Cl, —Br, —CF 3 , —N(CH 3 ) 2, —NHSO   2 CH 3 , and —NHCOCH 3 .  
 
 
     
     
         19 . A pharmaceutical composition comprising a compound from one of claims  1 - 18  and a pharmaceutically acceptable excipient.  
     
     
         20 . A pharmaceutical composition comprising a compound from one of claims  1 - 18 , a second agent, and a pharmaceutically acceptable excipient.  
     
     
         21 . A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims  1 - 18 .  
     
     
         22 . A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims  1 - 18  and an effective amount of a second agent.  
     
     
         23 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims  1 - 18 .  
     
     
         24 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims  1 - 18  and an effective amount of a second agent.