Inhibitors of HIF and angiogenesis

1. A compound of Formula I

or salt, ester, or prodrug thereof wherein,

is a single bond;

A is —CR 5 R 6 —, —CR 7 ═CR 8 —, or —CR 7 R 9 —CR 8 R 10 —;

E is O;

G is —SO 2 —;

X is CR 12 ;

Y is CR 13 ;

Z is N;

R 1 is alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R 1 is optionally substituted with one or more, the same or different, R 15 ;

R 2 is alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R 2 is optionally substituted with one or more, the same or different, R 16 ;

R 3 is alkyl optionally substituted with one or more, the same or different, R 17 ;

R 4 is R 4 is alkyl optionally substituted with one or more, the same or different, R 18 ;

R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are each individually and independently selected from hydrogen, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, optionally substituted with one or more, the same or different, R 19 ;

R 15 , R 16 , R 17 , R 18 , and R 19 are halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

2. The compound of claim 1 , wherein R 1 is a cyclopropyl, cyclobutyl or cyclopentyl.

3. The compound of claim 1 , wherein R 3 and R 4 are alkyl.

4. The compound of claim 1 , wherein R 3 is alkyl other than methyl.

5. The compound of claim 1 , wherein R 2 is 4-methoxyphenyl, 3,4-dimethoxyphenyl, or 3,5-dimethylphenyl.

6. The compound of claim 1 selected from the group:

N-cyclopentyl-N-((2,2-dimethyl-2H-pyrano[3,2-b]pyridin-6-yl)methyl)-3,4-dimethoxybenzenesulfonamide;

N-cyclobutyl-N-((2,2-dimethyl-2H-pyrano[3,2-b]pyridin-6-yl)methyl)-3,4-dimethoxybenzenesulfonamide;

or salts thereof.

7. A pharmaceutical compositions comprising a compound as provided in claim 1 or pharmaceutically acceptable salt and a pharmaceutically acceptable excipient.