Ureido substituted benzoic acid compounds and their use for nonsense suppression and the treatment of disease

1. A compound having the structure:

or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof, wherein:

X is C(═O), S, S(═O) or S(O) 2 ;

Y is aryl substituted with at least one heteroaryl or heterocyclo group, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocyclo;

R is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted aryl;

n is an integer ranging from 0-4;

R 1 and R 2 are each independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —(CH 2 ) m —W, carboxyalkyl, alkylcarbonyl, alkyloxyalkyl, alkyloxycarbonyl, arylalkyl, or R 1 and R 2 together with the atoms to which they are attached form an optionally substituted 5-7 membered heterocyclic, or heteroaryl ring or R 1 and R 2 together form:

W is at each occurrence independently hydrogen, halogen, hydroxy, alkoxy, carboxy, aldehyde, NH 2 , NR 14 R 14′ , nitro, cycloalkyl, heteroaryl, heteroarylalkyl;

where (i) each occurrence of R 14 and R 14′ is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or CF 3 ; or (ii) R 14 and R 14′ , together with the nitrogen atom to which they are bonded, join to form an optionally substituted heterocyclic ring containing from 5 to 8 ring atoms of which from 1 to 3 are heteroatoms;

m is an integer ranging from 1-4; and

R 16 is hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, carboxy, alkylcarboxy, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, substituted or unsubstituted heteroaryl, cyano, nitro, sulfonyl, alkoxy, haloalkoxy, alkylthio, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, alkylamino or aminoalkoxy.

2. A compound of claim 1 , wherein Y is:

wherein:

Q is at each occurrence independently C or N, optionally substituted with R 7 -R 11 where appropriate;

Z is at each occurrence independently C, N, O or S, optionally substituted with R 7 -R 11 where appropriate;

R 7 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, substituted or unsubstituted heteroaryl, cyano, nitro, haloalkoxy, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, or aminoalkoxy;

R 8 is hydrogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, alkylcarboxy, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, cyano, sulfonyl, alkoxy, haloalkoxy, alkylthio, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, alkylamino or aminoalkoxy;

R 9 is hydrogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, carboxy, alkylcarboxy, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, substituted or unsubstituted heteroaryl, cyano, sulfonyl, alkoxy, haloalkoxy, alkylthio, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, alkylamino or aminoalkoxy;

R 10 is hydrogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, alkylcarboxy, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, cyano, sulfonyl, alkoxy, haloalkoxy, alkylthio, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, alkylamino or aminoalkoxy;

R 11 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, substituted or unsubstituted heteroaryl, cyano, nitro, haloalkoxy, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, or aminoalkoxy; and

R 12 and R 13 are independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, carboxy, alkylcarboxy, carbonyl, alkylcarbonyl, substituted or unsubstituted aryl, alkylaryl, substituted or unsubstituted heterocyclo, substituted or unsubstituted heteroaryl, cyano, nitro, sulfonyl, alkoxy, haloalkoxy, alkylthio, alkylamino, alkoxycarbonyl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, alkylamino or aminoalkoxy,

wherein, when Y is phenyl or naphthyl, then at least one of R 7 , R 8 , R 9 , R 10 , R 11 , R 12 or R 13 is a substituted or unsubstituted heterocyclo.

3. A compound of claim 1 , wherein R 1 and R 2 together form:

4. A compound of claim 1 , wherein X is C(═O).

5. A compound of claim 4 , wherein R 1 and R 2 together form —CH 2 —CH 2 — or

6. A compound of claim 5 , wherein Y is substituted heteroaryl.

7. A compound of claim 5 , wherein Y is unsubstituted heteroaryl.

8. A compound of claim 5 , wherein Y is substituted heterocyclo.

9. A compound of claim 5 , wherein Y is unsubstituted heterocyclo.

10. A compound of claim 5 , wherein Y is aryl substituted with a substituted or unsubstituted heteroaryl group.

11. A compound of claim 5 , wherein Y is aryl substituted with a substituted or unsubstituted heterocyclo group.

12. A compound of claim 5 , wherein n is 0 or 1.

13. A compound of claim 1 having the structure:

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

14. A pharmaceutical composition comprising a compound of claim 1 and one or more carriers, excipients or diluents.

15. A pharmaceutical composition comprising a compound of claim 13 and one or more carriers, excipients or diluents.