2,3-substituted azaindole derivatives for treating viral infections
View Patent ↗The present invention relates to 2,3-Substituted Azaindole Derivatives, compositions comprising at least one 2,3-Substituted Azaindole Derivatives, and methods of using the 2,3-Substituted Azaindole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.
1. A compound having the formula:
or a pharmaceutically acceptable salt or ester thereof,
wherein:
Z 1 is —N—, —N(O)— or —C(R 4 )—;
Z 2 is —N—, —N(O)— or —C(R 5 )—;
Z 3 is —N—, —N(O)— or —C(R 6 )—;
Z 4 is —N—, —N(O)— or —C(R 7 )—, wherein one of Z 1 , Z 2 , Z 3 , and Z 4 is —N— and the others are not —N— or —N(O)—;
R 1 is —[C(R 12 ) 2 ] r ;
R 2 is —[C(R 12 ) 2 ] q —C(O)N(R 9 )SOR 11 , —[C(R 12 ) 2 ] q )—C(O)N(R)SO 2 R 11 , —[C(R 12 ) 2 ] q —C(O)N(R 9 )SO 2 N(R 11 ) 2 ,
R 3 is:
R 4 , R 5 , R 6 and R 7 are each, independently, H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 or —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 8 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;
each occurrence of R 9 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;
R 10 is aryl or heteroaryl, wherein an aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q -hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 11 is independently alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, haloalkyl, hydroxy or hydroxyalkyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from —H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 -alkyl, —[C(R 12 ) 2 ] q —NHSO 2 -cycloalkyl, —[C(R 12 ) 2 ] q —NHSO 2 aryl, —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 12 is independently H, halo, —N(R 9 ) 2 , —OR 9 , alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from alkyl, halo, haloalkyl, hydroxyalkyl, hydroxy, —CN, —C(O)alkyl, —C(O)Oalkyl, —C(O)NHalkyl, —C(O)N(alkyl) 2 , —O-alkyl, —NH 2 , —NH(alkyl), —N(alkyl) 2 , —NHC(O)alkyl, —NHSO 2 alkyl, —SO 2 alkyl or —SO 2 NH-alkyl, or two R 12 groups, together with the carbon atoms to which they are attached, join to form a cycloalkyl, heterocycloalkyl or C═O group;
each occurrence of R 30 is independently H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q cycloalkenyl, —[C(R 12 ) 2 ] q heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 or —SO 2 N(R 9 )C(O)N(R 9 ) 2 , or two adjacent R 30 groups, together with the carbon atoms to which they are attached, join to form a −3- to 7-membered ring selected from aryl, cycloalkyl, heteroaryl and heterocycloalkyl;
each occurrence of p is independently 0, 1 or 2;
each occurrence of q is independently an integer ranging from 0 to 4; and
each occurrence of r is independently an integer ranging from 1 to 4.
2. The compound of claim 1 , wherein R 2 is —C(O)N(R 9 )SOR 11 , —C(O)N(R 9 )SO 2 R 11 , —C(O)N(R 9 )SO 2 N(R 11 ) 2 or
wherein R 9 is H, alkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl and two R 20 groups join to form an aryl ring.
3. The compound of claim 2 , wherein R 1 is —CH 2 —, —CH 2 CH 2 —, —CH(CH 3 )— or
4. The compound of claim 2 , wherein one of Z 1 , Z 2 , Z 3 , and Z 4 is —N— and the others are not —N— or —N(O)—; R 4 and R 7 are each independently H, alkyl, halo or hydroxy, R 5 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN, and R 6 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN.
5. The compound of claim 2 , wherein R 10 is:
wherein R 13 is H, F, Br or Cl; R 14 represents up to 4 optional and additional substituents, each independently selected from alkyl, cycloalkyl, CF 3 , —CN, halo, —O-alkyl, —O-haloalkyl, —NHSO 2 -alkyl, —NO 2 , —C(O)NH 2 , —C(O)NH-alkyl, —C(O)OH, hydroxy, —NH 2 , —SO 2 alkyl, —SO 2 NHalkyl, —S-alkyl, —CH 2 NH 2 , —CH 2 OH, —SO 2 NH 2 , —NHC(O)-alkyl, —C(O)O-alkyl, —C(O)-heterocycloalkyl and heteroaryl; and
represents a pyridyl group, wherein the ring nitrogen atom can be at any of the five unsubstituted ring atom positions.
6. The compound of claim 5 , wherein R 4 and R 7 are each independently H, halo or hydroxy; R 5 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN; and R 6 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN.
7. A compound of claim 1 having the formula:
or a pharmaceutically acceptable salt or ester thereof,
wherein:
Z 1 is —N—, —N(O)— or —C(R 4 )—;
Z 2 is —N—, —N(O)— or —C(R 5 )—;
Z 3 is —N—, —N(O)— or —C(R 6 )—;
Z 4 is —N—, —N(O)— or —C(R 7 )—, such that one of Z 1 , Z 2 , Z 3 and Z 4 is —N— or —N(O)— and the others are not —N— or —N(O)—;
R 1 is —CH 2 —, —CH 2 CH 2 —, —CH(CH 3 )— or
R 2 is —C(O)N(R 9 )SOR 11 , —C(O)N(R 9 )SO 2 R 11 , or —C(O)N(R 9 )SO 2 N(R 11 ) 2 ;
R 3 is:
R 4 , R 5 , R 6 and R 7 are each, independently, H, alkyl, -cycloalkyl, -heterocycloalkyl, haloalkyl, halo, hydroxy, -Oalkyl, -Ohaloalkyl-NH 2 , —NH-alkyl or —N(alkyl) 2 ;
R 10 is:
each occurrence of R 11 is independently alkyl, aryl, cycloalkyl, haloalkyl, heteroaryl, heterocycloalkyl or hydroxyalkyl;
each occurrence of R 12 is independently H, halo, —N(alkyl) 2 , —OH, —O-alkyl, alkyl, cycloalkyl or heterocycloalkyl, or two R 12 groups, together with the carbon atoms to which they are attached, join to form a cycloalkyl, heterocycloalkyl or C═O group;
R 13 is H, F, Br or Cl;
R 14 represents up to 4 optional and additional substituents, each independently selected from alkyl, cycloalkyl, CF 3 , —CN, halo, —O-alkyl, —O-haloalkyl, —NHSO 2 -alkyl, —NO 2 , —C(O)NH 2 , —C(O)NH-alkyl, —C(O)OH, hydroxy, —NH 2 , —SO 2 alkyl, —SO 2 NHalkyl, —S-alkyl, —CH 2 NH 2 , —CH 2 OH, —SO 2 NH 2 , —NHC(O)-alkyl, —C(O)O-alkyl, —C(O)-heterocycloalkyl and heteroaryl;
each occurrence of R 30 is independently, H, halo, —N(alkyl) 2 , —OH, —O-alkyl, —O-haloalkyl, alkyl, cycloalkyl or heterocycloalkyl, or two adjacent R 30 groups, together with the carbon atoms to which they are attached, join to form a −3- to 7-membered ring selected from aryl, cycloalkyl, heteroaryl and heterocycloalkyl;
and
represents a pyridyl group, wherein the ring nitrogen atom can be at any of the five unsubstituted ring atom positions.
8. A compound having the formula:
or a pharmaceutically acceptable salt or ester thereof,
wherein:
Z 1 is —N—, —N(O)— or —C(R 4 )—;
Z 2 is —N—, —N(O)— or —C(R 5 )—;
Z 3 is —N—, —N(O)— or —C(R 6 )—;
Z 4 is —N—, —N(O)— or —C(R 7 )—, wherein one of Z 1 , Z 2 , Z 3 , and Z 4 is —N— and the others are not —N— or —N(O)—;
R 1 is —[C(R 12 ) 2 ] r ;
R 2 is —C(O)R 9 , —C(O)OR 9 , —C(O)OCH 2 OR 9 , —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , -alkyl, —[C(R 12 ) 2 ] q aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q cycloalkenyl, —[C(R 12 ) 2 ] q heterocycloalkyl, —[C(R 12 ) 2 ] q -heteroaryl or —[C(R 12 ) 2 ] q -heterocycloalkenyl, wherein an aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl or heteroaryl group can be optionally substituted with up to 4 substituents, which are the same or different, and are selected from alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q —haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
R 3 is:
R 4 , R 5 , R 6 and R 7 are each, independently, H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 or —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 8 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;
each occurrence of R 9 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;
R 10 is aryl or heteroaryl, wherein an aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q -hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 11 is independently alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, haloalkyl, hydroxy or hydroxyalkyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from —H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 alkyl, —[C(R 12 ) 2 ] q —NHSO 2 cycloalkyl, —[C(R 12 ) 2 ] q —NHSO 2 aryl, —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;
each occurrence of R 12 is independently H, halo, —N(R 9 ) 2 , —OR 9 , alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from alkyl, halo, haloalkyl, hydroxyalkyl, hydroxy, —CN, —C(O)alkyl, —C(O)Oalkyl, —C(O)NHalkyl, —C(O)N(alkyl) 2 , —O-alkyl, —NH 2 , —NH(alkyl), —N(alkyl) 2 , —NHC(O)alkyl, —NHSO 2 alkyl, —SO 2 alkyl or —SO 2 NH-alkyl, or two R 12 groups, together with the carbon atoms to which they are attached, join to form a cycloalkyl, heterocycloalkyl or C═O group;
each occurrence of R 30 is independently H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q cycloalkyl, —[C(R 12 ) 2 ] q cycloalkenyl, —[C(R 12 ) 2 ] q heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 or —SO 2 N(R 9 )C(O)N(R 9 ) 2 , or two adjacent R 30 groups, together with the carbon atoms to which they are attached, join to form a −3- to 7-membered ring selected from aryl, cycloalkyl, heteroaryl and heterocycloalkyl;
each occurrence of p is independently 0, 1 or 2;
each occurrence of q is independently an integer ranging from 0 to 4; and
each occurrence of r is independently an integer ranging from 1 to 4.
9. The compound of claim 8 , wherein R 2 is —C(O)OR 9 or —C(O)N(R 9 ) 2 , wherein R 9 is H, alkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl.
10. The compound of claim 9 , wherein each occurrence of R 30 is independently, H, halo, —N(alkyl) 2 , —OH, —O-alkyl, —O-haloalkyl, alkyl, cycloalkyl or heterocycloalkyl, or two adjacent R 30 groups, together with the carbon atoms to which they are attached, join to form an aryl, cycloalkyl, heteroaryl or heterocycloalkyl group.
11. The compound of claim 9 wherein R 1 is —CH 2 —, —CH 2 CH 2 —, —CH(CH 3 )— or
12. The compound of claim 9 , wherein one of Z 1 , Z 2 , Z 3 , and Z 4 is —N— and the others are not —N— or —N(O)—; and R 4 and R 7 are each independently H, alkyl, halo or hydroxy, R 5 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN, and R 6 is H, alkyl, —O-alkyl, —O-haloalkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, —NH 2 or —CN.
13. The compound of claim 8 , wherein R 10 is:
wherein R 13 is H, F, Br or Cl, R 14 represents up to 4 optional and additional substituents, each independently selected from alkyl, cycloalkyl, CF 3 , —CN, halo, —O-alkyl, —O-haloalkyl, —NHSO 2 -alkyl, —NO 2 , —C(O)NH 2 , —C(O)NH-alkyl, —C(O)OH, hydroxy, —NH 2 , —SO 2 alkyl, —SO 2 NHalkyl, —S-alkyl, —CH 2 NH 2 , —CH 2 OH, —SO 2 NH 2 , —NHC(O)-alkyl, —C(O)O-alkyl, —C(O)-heterocycloalkyl and heteroaryl, and
represents a pyridyl group, wherein the ring nitrogen atom can be at any of the five unsubstituted ring atom positions.
14. A compound having the structure:
or a pharmaceutically acceptable salt or ester thereof.
15. A composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt or ester thereof, and at least one pharmaceutically acceptable carrier.