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 a phosphatidyl ethanolamine comprising two C 14 -C 22 carboxylic acid groups each having one, two, three, or four sites of unsaturation, epoxidation, hydroxylation, or a combination thereof, each at a location of the respective carboxylic acid group carbon chain.
2. The composition of claim 1 wherein X 2 -R 3 is bonded to a carbon atom para to the methylene carbon bonded to the heteroaryl nitrogen atom.
3. The composition of claim 1 , wherein the two carboxylic acid groups of the phosphatidyl ethanolamine of the compound of Formula A are the same.
4. The composition of claim 1 , wherein either or both carboxylic acid groups of the phosphatidyl ethanolamine of the compound of Formula A is a C 17 carboxylic acid group with a site of unsaturation at C8-C9.
5. The composition of claim 1 , wherein either or both carboxylic acid groups of the phosphatidyl ethanolamine of the compound of Formula A is a C 18 carboxylic acid group with a site of unsaturation at C9-C10.
6. 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.
7. The composition of claim 1 , wherein for the compound of Formula A, R 1 is —(CH 2 ) 2 —OCH 3 .
8. The composition of claim 1 , which further comprises a liposome.
9. A composition comprising an amount of a compound of Formula A of claim 1 effective as an adjuvant.
10. A vaccine comprising an antigen and a compound of Formula A of claim 1 .
11. The composition of claim 1 , wherein the two carboxylic acid groups of phosphatidyl ethanolamine of the compound of Formula A are different.