Substituted pyrimidines as vaccine adjuvants
The present invention provides a compound of the formula (2): wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , Y 1 , Y 2 , and L are as defined in the description, and a pharmaceutically acceptable salt thereof, which are useful as a vaccine adjuvant.
1. A compound of the formula (2):
or a pharmaceutically acceptable salt thereof, wherein:
X is —CH 2 ;
Y 1 is —(CR 9 R 10 ) p —;
Y 2 is a single bond;
L is a straight chain C 2-6 alkylene, wherein the straight chain C 2-6 alkylene is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen and hydroxy;
R 1 is hydrogen or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of hydroxy halogen, and C 1-6 alkoxy;
R 2 is hydrogen or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, hydroxy, and C 1-6 alkoxy;
R 3 is C 1-6 alkyl;
R 4 is hydrogen, halogen, cyano, C 1-6 alkyl, hydroxy, or C 1-6 alkoxy;
R 5 is hydrogen or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of hydroxy and halogen;
R 6 is hydrogen or C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen and hydroxy;
R 8 is hydrogen or C(O)OC(CH 3 ) 3 ;
R 9 is hydrogen or C 1-4 alkyl;
R 10 is hydrogen or C 1-4 alkyl; and
p is 1, 2, 3, 4, 5, or 6.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
Y 1 is —CH 2 —;
L is a straight chain C 2-3 alkylene,
R 1 is hydrogen or C 1-3 alkyl, wherein the C 1-3 alkyl is optionally substituted with 1, 2, 3, or 4 hydroxy substituents;
R 2 is hydrogen or C 1-6 alkyl;
R 3 is C 1-3 alkyl;
R 4 is hydrogen, halogen, C 1-3 alkyl, hydroxy, or C 1-3 alkoxy;
R 5 is hydrogen or C 1-3 alkyl; and
R 6 is hydrogen or C 1-3 alkyl.
3. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 3 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 3 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.