Substituted pyrimidines

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

• R1 is CONRa(C1-2)alkyl-, a heteroarylene selected from isoxazoldiyl, pyrazoldiyl, imidazoldiyl, oxazoldiyl, thiazoldiyl, pyridindiyl, pyradizindiyl, and pyrimidindiyl;
• R2, R3, and R6 are each independently selected from hydrogen, hydroxy, and C1-6allyl;
• X is selected from —COOR, —PO(R′)OR, —PO(OR)2, —PO(NRR)2, —SO3R, —PO(C1-10alkyl)OR, PO(C3-10cycloalkyl)OR, PO(H)OR, and PO(NHCR′R″COOR)2
• R is independently selected from hydrogen, C1-10 alkyl, —C1-5 alkylaryl, —CR′R′—OCO—C1-10 alkyl, and CR′R′—OCO—OC1-10 alkyl;
• R′ and R″ are independently selected from hydrogen and C1-10 alkyl;
• L is selected from CONR6—, and NR6CO—;
• D is selected from hydrogen, aryl and heteroaryl;
• Ra, R4, and R5 are each independently selected from
• hydrogen,
• halogen,
• carboxyl C0-10 alkyl,
• C1-10 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C1-10 alkenylamino,
• C1-10 alkyl(oxy)0-1 carbonylC1-10 alkyl,
• aryl C0-10 alkyl(oxy)0-1 carbonylC1-10 alkyl,
• C3-8 cycloalkyl C0-10 alkyl(oxy)0-1carbonyl C1-10 alkyl,
• (C3-8)heterocyclyl C0-10 alkyl(oxy)0-1carbonyl C1-10 alkyl,
• (C3-8)heterocycloalkyl C0-10 alkyl(oxy)0-1 carbonyl C1-10 alkyl,
• arylC0-10 alkyl,
• C3-8 cycloalkyl C0-10 alkyl,
• C3-8 heterocyclyl C0-10 alkyl,
• C3-8 heterocycloalkyl C0-10 alkyl,
• C1-10 alkoxyl, and
• hydroxy C0-10alkyl;
• wherein, R1, Ra, R4, R5, and D are optionally substituted with 1, 2, or 3 substituent R7, selected from:
• halogen,
• (carbonyl)0-1C1-10 alkyl,
• (carbonyl)0-1C2-10 alkenyl,
• (carbonyl)0-1C2-10 alkynyl,
• C1-10 alkylcarbonyl,
• C2-10 alkenylcarbonyl,
• C2-10 alkynylcarbonyl,
• aryl C0-10 alkyl,
• (C3-8)heterocyclyl C0-10 alkyl,
• C3-8 cycloalkyl C0-10 alkyl,
• (C3-8)heterocycloalkyl C0-10 alkyl,
• C1-4acylamino C0-10 alkyl,
• C0-10 alkylamino C0-10 alkyl,
• arylC0-10 alkylamino C0-10 alkyl,
• C3-8 cycloalkyl C0-10 alkylamino C0-10 alkyl,
• C3-8 heterocyclyl C0-10 alkylamino C0-10 alkyl,
• C3-8 heterocycloalkyl C0-10 alkylamino C0-10 alkyl,
• C1-10alkyloxy C0-10alkyl,
• (C1-10 alkyl)2aminocarbonyloxy,
• hydroxy C0-10alkyl,
• C1-10 alkylsulfonyl,
• C1-10 alkylsulfonylamino,
• aryl C1-10 alkylsulfonylamino,
• C3-8 heterocyclyl C1-10 alkylsulfonylamino,
• C3-8 heterocycloalkyl C1-10 alkylsulfonylamino,
• C3-8 cycloalkyl C1-10 alkylsulfonylamino,
• cyano,
• nitro,
• perfluoroC1-6alkyl, and
• perfluoroC1-6alkoxy;
• wherein R7 is optionally substituted with 1, 2, or 3 substituents selected from hydrogen, hydroxy, (C1-6)alkoxyl, halogen, CO2H, CN, O(C═O)C1-C6 alkyl, NO2, trifluoromethoxy, trifluoroethoxy, —O(0-1)(C1-10)perfluoroalkyl, and NH2;
• and
• provided that when R1 is a heteroarylene, then X is other than —COOR.