Toll-like receptor modulators and uses thereof
View Patent ↗The present invention provides a compound of the formula: where n, m, X 1 , X 2 , X 3 , X 4 , R 1 , R 2 and R 3 are those defined herein. Some aspects of the invention also provides methods for using these compounds and compositions comprising the same.
1. A compound of the formula:
wherein
each of n and m is independently an integer from 0 to 5;
each X 1 is independently alkoxide, optionally-substituted alkyl, or alkenyl;
X 2 is O, NR a , or S;
X 3 is —OR b , —SR b , or —NR b R c ;
each X 4 is independently halide or alkoxide; and
each of R a , R b , R c , R 1 , R 2 , and R 3 is independently hydrogen or alkyl.
2. The compound according to claim 1 , wherein X 2 is O.
3. The compound according to claim 1 , wherein X 3 is —OH.
4. The compound according to claim 1 , wherein R 1 , R 2 and R 3 are alkyl.
5. The compound according to claim 4 , wherein R 1 , R 2 , and R 3 are methyl.
6. The compound according to claim 1 , wherein X 1 is alkoxide, hetero-substituted alkyl or alkenyl-alkyl.
7. The compound according to claim 1 , wherein X 4 is alkoxide, Cl, or F.
8. A method for inhibiting toll-like receptor 4 (TLR4) activity to treating pain or a unwanted opioid side-effect in a subject, said method comprising administering to the subject a compound of claim 1 .
9. The method of claim 8 , wherein said pain comprises chronic pain, nociception, or a combination thereof.
10. A composition comprising an opiate and a compound of claim 1 .
11. The composition of claim 10 , wherein said opiate and said compound of claim 1 are intimately mixed.
12. The composition of claim 10 , wherein the amount of said opiate is from about 50% to about 100% relative to the recommended dosage of said opiate in the absence of said compound of claim 1 .
13. The composition of claim 10 , wherein the mole ratio of said opiate to said compound of claim 1 ranges from about 1000:1 to about 10:1.