Pyrimidine compounds
This invention relates to a method for treating inflammatory diseases or immune diseases, developmental or degenerative diseases, or tissue injuries. The method includes administering to a subject in need thereof an effective amount of one or more compounds of formula (I). Each variable in this formula is defined in the specification.
1. A method for enhancing migration of bone marrow-derived cells to blood, comprising administering to a subject in need thereof an effective amount of a compound of formula (I):
wherein
X is —NH—;
each of L 1 and L 2 , independently, is C 1 -C 10 alkylene, —C(O)—, or deleted;
L 3 is —N(R b )—, —O—, aryl, heteroaryl, or C 3 -C 20 cycloalkyl;
R 1 is H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 3 -C 20 heterocycloalkyl, or NR c R d ;
R 2 is H, C 1 -C 10 alkyl, C 3 -C 20 heterocycloalkyl, halo, or CN;
R 3 is H, C 3 -C 20 heterocycloalkyl, halo, or NR c R d ;
R 4 is H; and
R 5 is
in which each of R b , R c , and R d , independently, is H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 3 -C 20 heterocycloalkyl, aryl, or heteroaryl.
2. The method of claim 1 , wherein L 3 is —N(R b )—.
3. The method of claim 2 , wherein R 1 is C 3 -C 20 heterocycloalkyl.
4. The method of claim 3 , wherein R 1 is
5. The method of claim 1 , wherein L 3 is aryl.
6. The method of claim 5 , wherein L 3 is phenylene.
7. The method of claim 1 , wherein L 3 is C 3 -C 20 cycloalkyl.
8. The method of claim 7 , wherein L 3 is cyclohexylene.
9. The method of claim 7 , wherein R 3 is C 3 -C 20 heterocycloalkyl substituted with C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 3 -C 20 heterocycloalkyl, aryl, OR′, C(O)R′, COOR′, C(O)N(R′R″), SO 2 R′, or C(S)N(R′R″), in which each of R′ and R″, independently, is H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 3 -C 20 heterocycloalkyl, aryl, or heteroaryl.
10. The method of claim 1 , wherein the bone marrow-derived cells are CD34+ cells or CD133+ cells.
11. The method of claim 1 , wherein the bone marrow-derived cells are stem cells or endothelial progenitor cells.
12. The method of claim 1 , further comprising concurrently administering to the subject an effective amount of a granulocyte-colony stimulating factor.
13. The method of claim 1 , further comprising administering to the subject an effective amount of a very later antigen-4 inhibitor.
14. The method of claim 1 , wherein R 3 is
wherein Q is C(O) or a bond, T is alkylene, and Y is OH or COOH.
15. The method of claim 1 , wherein the compound is one of the following compounds: