Conjugates of synthetic TLR agonists and uses therefor
The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.
1. A composition comprising a compound of formula A:
or a pharmaceutically acceptable salt thereof, wherein:
X 1 is —O—;
R 1 is hydrogen, (C 1 -C 10 )alkyl, or (C 1 -C 10 )alkyl substituted with (C 1 -C 6 )alkoxy;
X 2 is C(O); and
R 3 is dioleoylphosphatidyl ethanolamine (DOPE).
2. The composition of claim 1 wherein X 2 -R 3 is bonded to a carbon atom para to a methylene carbon bonded to a heteroaryl nitrogen atom
3. The composition of claim 1 wherein R 1 of the compound of Formula A is a (C 1 -C 10 )alkyl substituted with (C 1 -C 6 )alkoxy.
4. The composition of claim 1 wherein R 1 is —(CH 2 ) 2 —OCH 3 .
5. The composition of claim 1 wherein the compound of Formula A is a compound of formula
6. The composition of claim 1 which further comprises a liposome.
7. A composition comprising an amount of a compound of Formula A of claim 1 effective as an adjuvant.
8. A vaccine comprising an antigen and a compound of Formula A of claim 1 .