Compounds and their methods of use

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein:

X is a bond, —S—, —S(O)—, —SO 2 —, —CH═CH—, or —C(O)—;

each W, Y and Z is independently —S—, —CH═, —O—, —N═, or —NH—, provided that (1) at least one of W, Y and Z is not —CH═ and (2) when one of W is —S— and the Y in the same ring is N, then the Z in the same ring is not —CH═;

each R 1 and R 2 is independently C 1-6 alkylene-R 4 , N(R 3 )—C(O)—R 4 , —C(O)—N(R 3 )—R 4 , —N(R 3 )—C(O)—O—R 4 , —N(R 3 )—C(O)—N(R 3 )—R 4 , —O—C(O)—N(R 3 )—R 4 , —N(R 3 )—C(O)—C 1-6 alkylene-C(O)—R 4 , —N(R 3 )—C(O)—C 1-6 alkylene-N(R 3 )—C(O)—R 4 or —N(R 3a )—C(O)—CH 2 —N(R 3 )—C(O)—R 4 ;

each R 3 is independently hydrogen, C 1-6 alkyl or aryl;

each R 4 is independently C 1-6 alkyl, C 1-6 alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl, heterocyclyl, cycloalkyl or cycloalkylalkyl, each of which is substituted with 0-3 occurrences of R 5 , or two adjacent R 5 moieties, taken together with the atoms to which they are attached form a heterocyclyl, heteroaryl, cycloalkyl or aryl;

each R 5 is independently oxo (═O), C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, cyano, halo, —OH, —SH, —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 , —O—C(O)—C 1-6 alkyl, C 3-7 cycloalkyl, (C 3-7 cycloalkyl)alkyl, aryl, aryloxy, —C(O)-aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl or heterocyclyl, wherein each aryl, heteroaryl or heterocyclyl is further substituted with 0-3 occurrences of R 7 ;

each R 6 is independently hydrogen, OH or C 1-6 alkyl;

each R 7 is independently hydrogen, C 1-6 alkyl, —OH, —SH, cyano, halo, —CF 3 , —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 or C 1-6 alkoxy;

m is 1, 2 or 3;

n is 1, 2 or 3; provided that when X is bond, the sum of m and n is from 3 to 6 and when X is —S—, —S(O)—, —SO 2 —, —CH═CH—, or —C(O)—, the sum of m and n is from 2 to 4;

o is 1, 2 or 3; and

p is 1, 2 or 3;

with the proviso that:

(1) when X is —S—, m and n are both 2, each R 6 is H, then (i) R 1 and R 2 are not both —NHC(O)—R 4 , wherein R 4 is C 1-6 alkyl, monocyclic aryl, monocyclic heteroaryl, monocyclic aralkyl, monocyclic heteroaralkyl and each member of R 4 is substituted with 0-3 occurrences of R 5 ; and (ii) R 1 and R 2 are not both —NHC(O)O-methyl, —NHC(O)O-ethyl, —NHC(O)-6-pyrimidine-2,4(1H,3H)-dionyl, or —NHC(O)NH-phenyl wherein said phenyl of the —NHC(O)NH-phenyl moiety is optionally substituted with 1 or 2 groups selected from methyl, nitro, and halo;

(2) when X is —S—, m and n are both 1, each R 6 is H, then (i) R 1 and R 2 are not both —NH-phenyl or —NH-4-methoxy-phenyl;

(3) when X is a bond, the sum of m and n is 3, each R 6 is H, then R 1 and R 2 are not both NHC(O)-phenyl;

(4) when X is a bond, m and n are both 2, each R 6 is H, then R 1 and R 2 are not both —NHC(O)-furanyl, —NHC(O)-phenyl, —NHC(O)-o-methoxy-phenyl, —NHC(O)—C 1-6 alkyl, —NH-benzyl, or —NH-phenyl wherein said phenyl of the —NH-phenyl moiety is substituted with 0-3 occurrences of R 5 ;

(5) when X is a bond, the sum of m and n is 5, each R 6 is H, then R 1 and R 2 are not both —NHC(O)—C 1-6 alkyl, —NHC(O)-cyclohexyl, or —NH-phenyl wherein said phenyl of the —NH-phenyl moiety is optionally substituted with methyl; and

(6) when X is a bond, m and n are both 3, each R 6 is H, then R 1 and R 2 are not both NH-phenyl.

2. The compound of claim 1 , wherein each W is —S—, each Y is —N═ and each Z is —N═.

3. The compound of claim 1 , wherein each W is —CH═, each Z is —O— and each Y is —N═.

4. The compound of claim 1 , wherein o is 1 and p is 1.

5. The compound of claim 1 , wherein R 1 and R 2 are each —N(R 3 )—C(O)—O—R 4 , wherein R 3 is hydrogen.

6. The compound of claim 5 , wherein R 1 and R 2 are the same.

7. The compound of claim 1 , wherein the compound is a compound of Formula (II):

8. The compound of claim 6 , wherein R 1 and R 2 are the same.

9. The compound of claim 1 , wherein the compound is a compound of Formula (III):

10. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or adjuvant.

11. The compound of claim 1 , wherein the compound is selected from the group consisting of:

12. The compound of claim 1 , wherein the compound is selected from the group consisting of:

13. The compound of claim 1 , wherein the compound is selected from the group consisting of:

14. A compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein:

X is —S(O)— or —SO 2 —;

each W, Y and Z is independently —S—, —CH═, —O—, —N═, or —NH—, provided that (1) at least one of W, Y and Z is not —CH═ and (2) when one of W is —S— and the Y in the same ring is N, then the Z in the same ring is not —CH═;

each R 1 and R 2 is independently C 1-6 alkylene-R 4 , N(R 3 )—C(O)—R 4 , —C(O)—N(R 3 )—R 4 , —N(R 3 )—C(O)—O—R 4 , —N(R 3 )—C(O)—N(R 3 )—R 4 , —O—C(O)—N(R 3 )—R 4 , —N(R 3 )—C(O)—C 1-6 alkylene-C(O)—R 4 , —N(R 3 )—C(O)—C 1-6 alkylene-N(R 3 )—C(O)—R 4 or —N(R 3a )—C(O)—CH 2 —N(R 3 )—C(O)—R 4 ;

each R 3 is independently hydrogen, C 1-6 alkyl or aryl;

each R 4 is independently C 1-6 alkyl, C 1-6 alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl, heterocyclyl, cycloalkyl or cycloalkylalkyl, each of which is substituted with 0-3 occurrences of R 5 , or two adjacent R 5 moieties, taken together with the atoms to which they are attached form a heterocyclyl, heteroaryl, cycloalkyl or aryl;

each R 5 is independently oxo (═O), C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, cyano, halo, —OH, —SH, —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 , —O—C(O)—C 1-6 alkyl, C 3-7 cycloalkyl, (C 3-7 cycloalkyl)alkyl, aryl, aryloxy, —C(O)-aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl or heterocyclyl, wherein each aryl, heteroaryl or heterocyclyl is further substituted with 0-3 occurrences of R 7 ;

each R 6 is independently hydrogen, fluoro, —OH or C 1-6 alkyl;

each R 7 is independently hydrogen, C 1-6 alkyl, —OH, —SH, cyano, halo, —CF 3 , —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 or C 1-6 alkoxy;

m is 1, 2 or 3;

n is 1, 2 or 3; provided that when X is —S(O)— or —SO 2 —, the sum of m and n is from 2 to 4;

o is 1, 2 or 3; and

p is 1, 2or 3.

15. A pharmaceutical composition comprising a compound of claim 14 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or adjuvant.