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Details for Patent: 7,557,140

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Details for Patent: 7,557,140

Title:Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors
Abstract: This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q.sup.1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: --S(.dbd.O).sub.2NR.sup.1-- and --NR.sup.1S(.dbd.O).sub.2--; R.sup.1 is a sulfonamido substituent; and, Q.sup.2 is an acid leader group; with the proviso that if J is --S(.dbd.O).sub.2NR.sup.1--, then Q.sup.1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.
Inventor(s): Kalvinsh; Ivars (Riga, LV), Loza; Einars (Riga, LV), Gailite; Vija (Riga, LV)
Assignee: Topotarget UK Limited (Oxford, GB)
Filing Date:Feb 13, 2008
Application Number:12/030,397
Claims:1. A method for the treatment of rheumatoid arthritis comprising administering to a subject suffering from rheumatoid arthritis a therapeutically-effective amount of a compound selected from compounds of the following formula and pharmaceutically acceptable salts thereof: ##STR00393## wherein: A-Q.sup.1- is: ##STR00394## R.sup.1 is: hydrogen, C.sub.1-7alkyl, C.sub.3-20heterocyclyl, or C.sub.5-20aryl; and R.sup.Q2 is: a partially unsaturated aliphatic C.sub.2-7alkylene group, or a saturated aliphatic C.sub.2-7alkylene group.

2. A method according to claim 1, wherein R.sup.Q2 is a partially unsaturated aliphatic C.sub.2-7alkylene group.

3. A method according to claim 1, wherein R.sup.Q2 is a saturated aliphatic C.sub.2-7alkylene group.

4. A method according to claim 1, wherein R.sup.Q2 is --CH.dbd.CH--.

5. A method according to claim 1, wherein R.sup.Q2 is --(CH.sub.2).sub.2--.

6. A method for the treatment of rheumatoid arthritis comprising administering to a subject suffering from rheumatoid arthritis a therapeutically-effective amount of a compound selected from compounds of the following formula and pharmaceutically acceptable salts thereof: ##STR00395## wherein: A-Q.sup.1- is: ##STR00396## R.sup.1 is hydrogen, C.sub.1-7alkyl, C.sub.3-20heterocyclyl, or C.sub.5-20aryl.

7. A method according to claim 6, wherein A-Q.sup.1- is: ##STR00397##

8. A method according to claim 6, wherein A-Q.sup.1- is: ##STR00398##

9. A method according to claim 7, wherein R.sup.1 is --H, -Me, or -Et.

10. A method according to claim 8, wherein R.sup.1 is --H, -Me, or -Et.

11. A method according to claim 7, wherein R.sup.1 is --H.

12. A method for the treatment of rheumatoid arthritis comprising administering to a subject suffering from rheumatoid arthritis a therapeutically-effective amount of a compound selected from a compound of the following formula and pharmaceutically acceptable salts thereof: ##STR00399##

13. A method for the treatment of lupus comprising administering to a subject suffering from lupus a therapeutically-effective amount of a compound selected from compounds of the following formula and pharmaceutically acceptable salts thereof: ##STR00400## wherein: A-Q.sup.1- is: ##STR00401## R.sup.1 is: hydrogen, C.sub.1-7alkyl, C.sub.3-20heterocyclyl, or C.sub.5-20aryl; and R.sup.Q2 is: a partially unsaturated aliphatic C.sub.2-7alkylene group, or a saturated aliphatic C.sub.2-7alkylene group.

14. A method according to claim 13, wherein R.sup.Q2 is a partially unsaturated aliphatic C.sub.2-7alkylene group.

15. A method according to claim 13, wherein R.sup.Q2 is a saturated aliphatic C.sub.2-7alkylene group.

16. A method according to claim 13, wherein R.sup.Q2 is --CH.dbd.CH--.

17. A method according to claim 13, wherein R.sup.Q2 is --(CH.sub.2).sub.2--.

18. A method for the treatment of lupus comprising administering to a subject suffering from lupus a therapeutically-effective amount of a compound selected from compounds of the following formula and pharmaceutically acceptable salts thereof: ##STR00402## wherein: A-Q.sup.1- is: ##STR00403## R.sup.1 is hydrogen, C.sub.1-7alkyl, C.sub.3-20heterocyclyl, or C.sub.5-20aryl.

19. A method according to claim 18, wherein A-Q.sup.1- is: ##STR00404##

20. A method according to claim 18, wherein A-Q.sup.1- is: ##STR00405##

21. A method according to claim 19, wherein R.sup.1 is --H, -Me, or -Et.

22. A method according to claim 20, wherein R.sup.1 is --H, -Me, or -Et.

23. A method according to claim 19, wherein R.sup.1 is --H.

24. A method for the treatment of lupus comprising administering to a subject suffering from lupus a therapeutically-effective amount of a compound selected from a compound of the following formula and pharmaceutically acceptable salts thereof: ##STR00406##
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