Compounds and methods for treatment of systemic lupus erythematosus
View Patent ↗Small molecule compounds are provided for treating lupus as are methods of treating lupus using these compounds.
1. A compound having the structure:
wherein:
m=1-6;
R 1 is quinoline or isoquinoline, partially or fully hydrated, and optionally substituted with R′, OR′, SR′, (CH 2 ) n′ NHR′ or (CH 2 ) n′ N(R′) 2 , wherein n′=0-6, and R′ is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl;
R 2 is (i) keto or thioketo; or (ii) R″, OR″, SR″, NHR″ or N(R″) 2 , wherein R″ is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl;
R 3 and R 4 are, independently, H or (CH 2 ) n R where R is aryl and n=1-6;
R 5 is (CH 2 ) n′″ N(R 3 ) 2 or (CH 2 ) n′″ COX wherein X is R′″, OR′″, SR′″, NHR′″ or N(R′″) 2 , wherein n′″=0-6, and R′″ is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl; and
R 6 is quinoline or isoquinoline, partially or fully hydrated, and optionally substituted with R IV , OR IV , SR IV , (CH 2 ) N IV NHR IV or (CH 2 ) n IV N(R IV ) 2 , wherein n IV =0-6, and R IV is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 1 is isoquinoline, partially or fully hydrated, and optionally substituted with R′, OR′, SR′, (CH 2 ) n′ NHR′ or (CH 2 ) n′ N(R) 2 , wherein n′=0-6, and R′ is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl.
3. The compound of claim 2 , wherein in R 1 , isoquinoline is fully hydrated.
4. The compound of claim 1 , wherein in R 1 , isoquinoline is substituted with (CH 2 ) n′ NHR′ or CH 2 NHR′.
5. The compound of claim 1 , wherein R′ is branched or unbranched C 1-6 alkyl.
6. The compound of claim 1 , wherein R′ is branched C 4 alkyl.
7. The compound of claim 1 , wherein R 1 has the structure
where ( ) represents the point of attachment to the molecular scaffold.
8. The compound of claim 1 , wherein R 2 is R″ or OR″.
9. The compound of claim 1 , wherein R 2 is OH.
10. The compound of claim 1 , wherein R 3 is (CH 2 ) n R.
11. The compound of claim 1 , wherein R 3 is benzyl.
12. The compound of claim 1 , wherein R 4 is H.
13. The compound of claim 1 , wherein R 5 is (CH 2 ) n′″ N(R 3 ) 2 .
14. The compound of claim 1 , wherein R 5 is (CH 2 ) 2 NH 2 .
15. The compound of claim 1 , wherein m=1.
16. The compound of claim 1 , wherein R 6 is quinoline, partially or fully hydrated, and optionally substituted with R IV , OR IV , SR IV , (CH 2 ) n IV NHR IV or (CH 2 ) n IV N(R IV ) 2 , wherein n IV =0-6, and R IV is independently H, or branched or unbranched C 1-6 alkyl or heteroalkyl.
17. The compound of claim 1 , wherein in R 6 , quinoline is partially hydrated.
18. The compound of claim 1 , wherein in R 6 , the partially hydrated quinoline is 1,2,3,4-tetrahydroquinoline.
19. The compound of claim 1 , wherein in R 6 , quinoline is substituted with R IV or OR IV .
20. The compound of claim 1 , wherein in R 6 , quinoline is substituted with OH.
21. The compound of claim 1 , wherein R 6 has the structure
where ( ) represents the point of attachment to the molecular scaffold.
22. The compound of claim 1 having the structure
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 1 , wherein the compound is tagged with a radioisotope or a toxin.
24. The compound of claim 1 , wherein the compound is coupled to an antibody or Fc backbone.
25. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
26. A method of treating systemic lupus erythematosus (SLE) in a subject comprising administering the compound of claim 1 to the subject in an amount and manner effective to treat SLE.