Substituted pyrimidines

1. A compound of formula I and pharmaceutically acceptable salts and solvates thereof

R 1 is —CONR a (C 1-2 )alkyl-, a heteroarylene selected from isoxazoldiyl, pyrazoldiyl, imidazoldiyl, oxazoldiyl, thiazoldiyl, pyridindiyl, pyradizindiyl, and pyrimidindiyl;

R 2 , R 3 , and R 6 are each independently selected from hydrogen, hydroxy, and C 1-6 alkyl;

X is selected from —COOR, —PO(R′)OR, —PO(OR) 2 , —PO(NRR) 2 , —SO 3 R, —PO(C 1-10 alkyl)OR, PO(C 3-10 cycloalkyl)OR, PO(H)OR, and PO(NHCR′R″COOR) 2

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—OC 1-10 alkyl;

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

L is selected from —CONR 6 —, and —NR 6 CO—;

D is selected from hydrogen, aryl and heteroaryl;

R a , R 4 , and R 5 are each independently selected from

hydrogen,

halogen,

caboxyl 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,

arylC 0-10 alkyl,

C 3-8 cycloalkyl C 0-10 alkyl,

C 3-8 heterocyclyl C 0-10 alkyl,

C 3-8 heterocycloalkyl C 0-10 alkyl,

C 1-10 alkoxyl, and

hydroxy C 0-10 alkyl;

wherein, R 1 , R a , R 4 , R 5 , and D are optionally substituted with 1, 2, or 3 substituent R 7 , selected 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,

arylC 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)2aminocarbonyloxy,

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 7 is optionally substituted with 1, 2, or 3 substituents selected 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 R 1 is a heteroarylene, then X is other than —COOR.

2. A compound of claim 1 wherein R 1 is —CONR a (C 1-2 )alkyl-, optionally substituted with 1, 2, or 3 R 7 substituents.

3. A compound of claim 1 wherein R 1 is a heteroarylene selected from isoxazoldiyl, imidazoldiyl, oxazoldiyl, pyridindiyl, and pyrimidindiyl, optionally substituted with 1, 2, or 3 R 7 substituents.

4. A compound of claim 1 wherein R 2 is hydroxy.

5. A compound of claim 1 wherein R 3 is hydrogen.

6. A compound of claim 1 wherein R 6 is hydrogen.

7. A compound of claim 1 , wherein R a , R 4 , and R 5 are each independently selected from hydrogen, arylC 0-10 alkyl, C 3-8 cycloalkyl C 0-10 alkyl, C 3-8 heterocyclyl C 0-10 alkyl, C 3-8 heterocycloalkylC 0-10 alkyl, and hydroxyC 0-10 alkyl; wherein R a , R 4 , and R 5 are each optionally substituted by 1, 2, or 3 R 7 substituents.

8. A compound of claim 7 , wherein R a , R 4 , and R 5 are selected from: hydrogen, halogen, and C 1-10 alkyl.

9. A compound of claim 3 , wherein R 1 is selected from isoxazoldiyl, imidazoldiyl, and oxazoldiyl, optionally substituted with 1, 2, or 3 R 7 substituents.

10. A compound of claim 1 , wherein substituent R 7 is selected from: halogen, (carbonyl) 0-1 C 1-10 alkyl, 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 1-10 alkyloxy C 0-10 alkyl, hydroxy C 0-10 alkyl, C 1-10 alkylsulfonyl, cyano, nitro, perfluoroC 1-6 alkyl, and perfluoroC 1-6 alkoxy.

11. A compound of claim 10 , wherein substituent R 7 is selected from: halogen, (carbonyl) 0-1 C 1-10 alkyl, C 1-10 alkyloxy C 0-10 alkyl, hydroxy C 0-10 alkyl, cyano, nitro, perfluoroC 1-6 alkyl, and perfluoroC 1-6 alkoxy.

12. A compound selected from:

1-(5-(benzhydrylcarbamoyl)-4-hydroxypyrimidin-2-yl)-1H-pyrazol-4-yl(methyl)phosphinic acid;

Ethyl N-({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)-β-alaninate;

Ethyl N-({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)glycinate;

Methyl N-({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)glycinate;

2-[({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)amino]ethanesulfonic acid;

Diethyl {[({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)amino]methyl}phosphonate;

Ethyl {[({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)amino]methyl}methylphosphinate;

Benzyl N-({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)glycinate;

3-(5-(benzhydrylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)propanoic acid;

2-(5-(benzhydrylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)acetic acid;

{[({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)amino]methyl}phosphonic acid;

{[({5-[(diphenylmethyl)carbamoyl]-4-hydroxypyrimidin-2-yl}carbonyl)amino]methyl}methylphosphinic acid;

2-(5-(bis(4-methoxyphenyl)methylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)acetic acid;

Ethyl-2-(5-(bis(4-fluorophenyl)methylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)acetate;

2-(5-(bis(4-fluorophenyl)methylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido) acetic acid;

Ethyl-2-(4-hydroxy-5-(naphthalen-1-ylmethylcarbamoyl)pyrimidine-2-carboxamido)acetate;

2-(4-hydroxy-5-(naphthalen-1-ylmethylcarbamoyl)pyrimidine-2-carboxamido)acetic acid;

N-({4-hydroxy-5-[(naphthalen-2-ylmethyl)carbamoyl]pyrimidin-2-yl}carbonyl)glycine;

2-(5-(2,2-Diphenylacetamido)-4-hydroxypyrimidine-2-carboxamido)acetic acid;

and pharmaceutically acceptable salts and solvates thereof.

13. A compound selected from:

2-(5-(bis(4-methoxyphenyl)methylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)acetic acid;

3-(5-(benzhydrylcarbamoyl)-4-hydroxypyrimidine-2-carboxamido)propanoic acid;

and pharmaceutically acceptable salts and solvates thereof.

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

15. 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 or solvate thereof.