Substituted pyrimidines

1. A compound of formula I or pharmaceutically acceptable salts thereof:

R 1 is a heteroaryl selected from isoxazolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridinyl, pyradizinyl, and pyrimidinyl;

R 2 and R 3 are each independently chosen from hydrogen, hydroxy, —OR, —OCOR, —OCOOR, —OCONHR, and C 1-6 alkyl;

X is selected from —(C 0-3 alkyl)PO(R′)OR, —(C 0-3 alkyl)PO(OR) 2 , —(C 0-3 alkyl)PO(NRR) 2 , —SO 3 R,

—(C 0-3 alkyl)PO(C 1-10 alkyl)OR, —(C 0-3 alkyl)PO(C 3-10 cycloalkyl)OR,

—(C 0-3 alkyl)PO(H)OR, —(C 0-3 alkyl)PO(NHCR′R″COOR) 2 and —COOR;

R is independently selected from hydrogen, C 1-10 alkyl, —C 1-5 alkylaryl, —CR′R′-OCO—C 1-10 alkyl, and

—CR′R′—OCO—O—C 1-10 alkyl;

R′ and R″ are independently selected from hydrogen and C 1-10 alkyl;

L is chosen from a bond, —CONR 4 —, —NR 4 CO—, aryl, and heteroaryl;

D is chosen from a bond, aryl, and heteroaryl, provided that when L is a bond then D is aryl or heteroaryl;

R 4 , R 6 , and R 7 are each independently selected from

hydrogen,

halogen,

carboxyl C 0-10 alkyl,

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl,

C 1-10 alkenylamino,

C 1-10 alkyl(oxy) 0-1 carbonylC 1-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 carbonylC 1-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl(oxy) 0-1 carbonyl C 1-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl(oxy) 0-1 carbonyl C 1-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 carbonyl C 1-10 alkyl,

aryl(oxy) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl(oxy) 0-1 C 0-10 alkyl,

C 3-8 heterocyclyl(oxy) 0-1 C 0-10 alkyl,

C 3-8 heterocycloalkyl (oxy) 0-1 C 0-10 alkyl,

C 1-10 alkoxyl,

arylC 1-10 alkoxyl, and

hydroxyC 0-10 alkyl;

wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and D are optionally substituted with 1, 2, or 3 substituent R 5 chosen from:

halogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 1-10 alkylcarbonyl,

C 2-10 alkenylcarbonyl,

C 2-10 alkynylcarbonyl,

aryl C 0-10 alkyl,

(C 3-8 )heterocyclyl C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

(C 3-8 )heterocycloalkyl C 0-10 alkyl,

C 1-4 acylamino C 0-10 alkyl,

C 0-10 alkylamino C 0-10 alkyl,

arylC 0-10 alkylamino C 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkylamino C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkylamino C 0-10 alkyl,

C 1-10 alkyloxy C 0-10 alkyl,

(C 1-10 alkyl) 2 aminocarbonyloxy,

hydroxy C 0-10 alkyl,

C 1-10 alkylsulfonyl,

C 1-10 alkylsulfonylamino,

aryl C 1-10 alkylsulfonylamino,

C 3-8 heterocyclyl C 1-10 alkylsulfonylamino,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonylamino,

C 3-8 cycloalkyl C 1-10 alkylsulfonylamino,

cyano,

nitro,

perfluoroC 1-6 alkyl, and

perfluoroC 1-6 alkoxy;

wherein R 5 is optionally substituted with 1, 2, or 3 substituents chosen from hydrogen, hydroxy, (C 1-6 )alkoxyl, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, NO 2 , trifluoromethoxy, trifluoroethoxy, —O (0-1) (C 1-10 )perfluoroalkyl, and NH 2 ; and

provided that when X is —COOR then L is isoxazoldiyl and D is phenyl.

2. A compound according to claim 1 , wherein:

X is selected from —(C 0-3 alkyl)PO(R′)OR, —(C 0-3 alkyl)PO(OR) 2 , —(C 0-3 alkyl)PO(NRR) 2 , —SO 3 R, —(C 0-3 alkyl)PO(C 1-10 alkyl)OR, —(C 0-3 alkyl)PO(C 3-10 cycloalkyl)OR, —(C 0-3 alkyl)PO(H)OR, and —(C 0-3 alkyl)PO(NHCR′R″COOR) 2 ; and R 2 and R 3 are each independently chosen from hydrogen, hydroxy, and C 1-6 alkyl.

3. A compound according to claim 2 , wherein L is —CONR 4 —, or —NR 4 CO—.

4. A compound according to claim 2 , wherein L is a bond, aryl, or heteroaryl.

5. A compound according to claim 4 , wherein L is heteroaryl.

6. A compound according to claim 5 , wherein L is chosen from isoxazoldiyl, oxazoldiyl, pyrazoldiyl, imidazoldiyl, thazoldiyl, pyridindiyl, pyradizindiyl, and pyrimidindiyl.

7. A compound according to claim 6 , wherein L is isoxazoldiyl.

8. A compound according to claim 2 , wherein R 1 is selected from isoxazolyl, imidazolyl, oxazolyl, pyridinyl, pyradizinyl, and pyrimidinyl, optionally substituted with 1, 2, or 3 R 5 substituents.

9. A compound according to claim 8 , wherein R 1 is selected from pyridindiyl, pyradizindiyl, and pyrimidindiyl, optionally substituted with 1, 2, or 3 R 5 substituents.

10. A compound according to claim 2 , wherein R 2 is hydroxy.

11. A compound according to claim 6 , wherein R 3 is hydrogen.

12. A compound according to claim 1 , wherein R 4 , R 6 , and R 7 are each independently selected from hydrogen, aryl C 0-10 alkyl, (C 3-8 )heterocyclylC 0-10 alkyl, C 3-8 cycloalkylC 0-10 alkyl, (C 3-8 )heterocycloalkylC 0-10 alkyl, C 1-10 alkyl, hydroxyC 0-10 alkyl, and arylC 1-10 alkoxyl.

13. A compound according to claim 12 , wherein R 4 , R 6 , and R 7 are each independently selected from napthalenyl, phenylmethoxy, phenyl, methyl, ethyl, propyl, cyclohexyl, and hydrogen.

14. A compound selected from:

diethyl 4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphonate;

4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphonic acid;

(2S,2′S)-diethyl 2,2′-((4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenyl)phosphoryl)bis(azanediyl)dipropanoate;

diethyl 2,2′-((4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenyl)phosphoryl)bis(azanediyl)bis(2-methylpropanoate);

diethyl 2,2′-((4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenyl)phosphoryl)bis(azanediyl)diacetate;

4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphinic acid;

Diethyl 4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl phosphonate;

4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl phosphonic acid;

Ethyl 4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenylphosphonate;

ethyl 4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinate;

4-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

diethyl 4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenyl phosphonate;

4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

ethyl hydrogen 4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonate;

diethyl (R)-4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenyl phosphonate;

(R)-4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

diethyl (S)-4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenyl phosphonate;

(S)-4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

(S)-4-(1-(4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

diethyl 5-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)pyridin-2-ylphosphonate;

ethyl hydrogen 5-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl)pyridin-2-ylphosphonate;

3-((4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphonic acid;

diisopropyl (4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methyl phosphonate;

isopropyl Hydrogen (4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methylphosphonate;

isopropyl Hydrogen (4-hydroxy-2-(pyridin-2-yl)pyrimidine-5-carboxamido)(phenyl)methylphosphonate;

diethyl 4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidin-5-ylamino)-1-oxopropan-2-yl)phenyl phosphonate;

ethyl 4-(1-(4-hydroxy-2-(pyridin-2-yl)pyrimidin-5-ylamino)-1-oxopropan-2-yl)phenylphosphonate;

diethyl 4-((4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenylphosphonate;

ethyl hydrogen 4-((4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenylphosphonate;

ethyl 4-((4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinate;

4-((4-Hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

diethyl 4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenylphosphonate;

4-((4-Hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphinic acid;

4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphinic acid;

diethyl (4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methylphosphonate;

diethyl 4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylamino)-1-oxopropan-2-yl)phenylphosphonate;

diethyl 4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylamino)-2-methyl-1-oxopropan-2-yl)phenylphosphonate;

diethyl 4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylamino)-3-methyl-1-oxobutan-2-yl)phenylphosphonate;

diethyl 4-(2-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidin-5-ylamino)-2-oxo-1-phenylethyl)phenylphosphonate;

diethyl 4-(2-(4-hydroxy-2-(pyridazin-3-yl)pyrimidin-5-ylamino)-2-oxo-1-phenylethyl)phenylphosphonate;

4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

(R)-4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)ethyl)phenyl phosphonic acid;

(S)-4-(1-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)ethyl)phenylphosphonic acid;

4-((4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(propyl)phosphinic acid;

4-((4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((R)-(4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((S)-(4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((R)-(2,4-difluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((S)-(2,4-difluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((S)-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

4-((R)-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

3-((R)-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

3-((S)-(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)(phenyl)methyl)phenyl(methyl)phosphinic acid;

4-((R)-cyclohexyl(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((S)-cyclohexyl(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinic acid;

4-((S)-(2-(4-fluoro-1H-pyrazol-1-yl)-4-hydroxypyrimidine-5-carboxamido)(4-fluorophenyl)methyl)phenyl(methyl)phosphinic acid;

4-((R)-(2-(4-fluoro-1H-pyrazol-1-yl)-4-hydroxypyrimidine-5-carboxamido)(4-fluorophenyl)methyl)phenyl(methyl)phosphinic acid;

(4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(phenyl)methylphosphonic acid;

(4-Hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl phosphonic acid;

(4-Hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(naphthalen-2-yl)methyl phosphonic acid;

diethyl 2,2′-((4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenyl)phosphoryl)bis(azanediyl)diacetate;

(2S,2′S)-Diethyl 2,2′-((4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenyl)phosphoryl)bis(azanediyl)dipropanoate;

4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)benzylphosphonic acid;

4-(5-(2-(4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)propan-2-yl)pyridine-2-yl)phenylphosphonic acid;

3-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)phenylphosphonic acid;

3-(2-(4-hydroxy-2-(pyridazin-3-yl)pyrimidin-5-ylamino)-2-oxoethyl)phenyl phosphonic acid;

(4-Hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl phosphonic acid;

4-(5-(4-Hydroxy-2-(pyridin-2-yl)pyrimidin-5-yl)isoxazol-3-yl)benzoic acid; and

4-(5-(4-hydroxy-2-(pyridin-2-yl)pyrimidin-5-yl)isoxazol-3-yl)phenyl(methyl)phosphinic acid; or pharmaceutically acceptable salts, thereof.

15. A pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable carrier.

16. A method for the treatment of anemia in a mammal which comprises administering to the mammal an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.