Fatty acid derivatives and their use
View Patent ↗This disclosure concerns fatty acid derivatives, pharmaceutical compositions comprising the fatty acid derivatives, and methods of using the fatty acid derivatives, for example, to treat inflammation, chronic itch, chronic pain, an autoimmune disorder, atherosclerosis, a skin disorder, arthritis, a neurodegenerative disorder, or a psychiatric disorder in a subject. In some embodiments, the fatty acid derivative is a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a structure according to: wherein X is from 1-16 carbons in length, Z is aliphatic from 1-16 carbons in length, or is not present, Y is selected from: R 1 , R 2 , and R 3 are independently hydrogen or lower alkyl, R 4 is lower alkyl, hydroxyl, carboxyl, or amine, R 5 is hydrogen, lower alkyl, or halide, R 6 is hydroxyl or substituted thiol, and each R 7 is independently hydrogen or fluoride or is not present and the adjacent carbons form alkyne.
1. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a structure according to:
wherein
X is halogenated alkenyl or deuterium-substituted alkenyl, from 10-25 carbons in length and is substituted with one or more hydroxyl or carbonyl substitutions;
R 1 is hydrogen or C 1 -C 10 alkyl; and
each R 2 is methyl.
2. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a structure according to any one of formulas:
wherein
R 1 is hydrogen or C 1 -C 10 alkyl,
R 2 and R 3 independently are C 1 -C 10 alkyl,
R 4 is C 1 -C 10 alkyl,
R 5 is hydrogen,
R 6 is hydroxyl,
each R 7 is independently hydrogen or is not present and the adjacent carbon atoms form an alkyne, and, if present,
each R 8 is independently hydrogen or fluoride, and
each R 9 is independently hydrogen or deuterium.
3. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is:
4. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a structure according to one of:
wherein:
R 5 is hydrogen, C 1 -C 10 alkyl, or halide;
each R 7 is independently hydrogen or fluoride or not present and the adjacent carbons form alkyne; and
R 10 and R 11 are independently C 1 -C 10 aliphatic.
5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 5 , formulated for topical, parenteral, or oral administration.
7. The compound of claim 2 , having a structure according to formula LXX:
8. The compound of claim 7 , wherein R 1 is hydrogen.
9. The compound of claim 7 , wherein R 2 , R 3 , and R 4 are methyl.
10. The compound of claim 1 , wherein X is substituted with one or more hydroxyl substitutions.
11. The compound of claim 1 , wherein X is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 carbons in length.
12. A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, having a structure according to:
wherein
X is aliphatic from 1-16 carbons in length,
Z is aliphatic from 1-16 carbons in length, or is not present,
Y is selected from
R 1 is hydrogen or C 1 -C 10 alkyl;
R 2 and R 3 independently are C 1 -C 10 alkyl;
R 4 is C 1 -C 10 alkyl;
R 5 is hydrogen;
R 6 is hydroxyl; and
each R 7 is independently hydrogen or is not present and the adjacent carbon atoms form an alkyne.
13. A pharmaceutical composition comprising a compound of claim 12 and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , formulated for topical, parenteral, or oral administration.
15. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
16. The pharmaceutical composition of claim 15 , formulated for topical, parenteral, or oral administration.