Details for Patent: 7,407,988

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: (1) 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 (Abingdon, GB)
Filing Date:	Sep 07, 2006
Application Number:	11/516,620
Claims:	1. A compound selected from compounds of the following formula and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof: ##STR00391## wherein: A-Q.sup.1- is: ##STR00392## 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 compound according to claim 1, wherein R.sup.Q2 is a partially unsaturated aliphatic C.sub.2-7alkylene group. 3. A compound according to claim 1, wherein R.sup.Q2 is a saturated aliphatic C.sub.2-7alkylene group. 4. A compound according to claim 1, wherein R.sup.Q2 is --CH.dbd.CH--. 5. A compound according to claim 1, wherein R.sup.Q2 is --(CH.sub.2).sub.2--. 6. A compound selected from compounds of the following formula and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs 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. 7. A compound according to claim 6, wherein A-Q.sup.1- is: ##STR00395## 8. A compound according to claim 6, wherein A-Q.sup.1- is: ##STR00396## 9. A compound according to claim 7, wherein R.sup.1 is --H, -Me, or -Et. 10. A compound according to claim 8, wherein R.sup.1 is --H, -Me, or -Et. 11. A compound selected from compounds of the following formula and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof: ##STR00397## wherein A-Q.sup.1- is: ##STR00398## 12. A compound according to claim 11, wherein A-Q.sup.1- is: ##STR00399## 13. A compound selected from a compound of the following formula and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof: ##STR00400## 14. A compound selected from compounds of the following formula and pharmaceutically acceptable salts and solvates thereof: ##STR00401## wherein A-Q.sup.1- is: ##STR00402## 15. A compound selected from a compound of the following formula and pharmaceutically acceptable salts and solvates thereof: ##STR00403## 16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent. 17. A pharmaceutical composition comprising a compound according to claim 6 and a pharmaceutically acceptable carrier or diluent. 18. A pharmaceutical composition comprising a compound according to claim 14 and a pharmaceutically acceptable carrier or diluent. 19. A pharmaceutical composition comprising a compound according to claim 15 and a pharmaceutically acceptable carrier or diluent. 20. A method inhibiting HDAC in a cell comprising said cell with an effective amount of a compound according to claim 1. 21. A method for the treatment of cancer comprising administering to a subject suffering from cancer a therapeutically-effective amount of a compound according to claim 1. 22. A method for the treatment of psoriasis comprising administering to a subject suffering from psoriasis a therapeutically-effective amount of a compound according to claim 1.