Claims for Patent: 6,888,027

Summary for Patent: 6,888,027

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.2 NR.sup.1 -- and --NR.sup.1 S(.dbd.O).sub.2 --; R1 is a sulfonamido substituent; and, Q.sup.2 is an acid leader group; with the proviso that if J is --S(.dbd.O).sub.2 NR.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. ##STR1##
Inventor(s):	Watkins; Clare J (Abingdon, GB), Romero-Martin; Maria Rosario (Didcot, GB), Moore; Kathryn G (Abingdon, GB), Ritchie; James (Abingdon, GB), Finn; Paul W (Abingdon, GB), Kalvinsh; Ivars (Riga, LV), Loza; Einars (Riga, LV), Dikovska; Klara (Riga, LV), Gailite; Vija (Riga, LV), Vorona; Maxim (Riga, LV), Piskunova; Irina (Riga, LV), Starchenkov; Igor (Riga, LV), Andrianov; Victor (Riga, LV), Harris; C. John (Sittingbourne, GB), Duffy; James E. S. (Sittingbourne, GB)
Assignee:	Topotarget UK Limited (Abingdon, GB)
Application Number:	10/381,790
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,888,027
Patent Claims:	1. A compound of the formula: ##STR404## wherein: A is an unsubstituted phenyl group; Q.sup.1 is a covalent bond or a C.sub.1-7 alkylene group; J is: ##STR405## R.sup.1 is hydrogen, C.sub.1-7 alkyl, C.sub.3-20 heterocyclyl, or C.sub.5-20 aryl; and, Q.sup.2 is: ##STR406## and pharmaceutically acceptable salts thereof. 2. A compound according to claim 1, wherein Q.sup.1 is a covalent bond. 3. A compound according to claim 1, wherein Q.sup.1 is a C.sub.1-7 alkylene group. 4. A compound according to claim 1, wherein Q.sup.1 is: a saturated linear C.sub.1-7 alkylene group, a saturated branched C.sub.1-7 alkylene group, a partially unsaturated linear C.sub.1-7 alkylene group, or a partially unsaturated branched C.sub.1-7 alkylene group. 5. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 --. 6. A compound according to claim 1, wherein Q.sup.1 is --CH(CH.sub.3)--. 7. A compound according to claim 1, wherein Q.sup.1 is --CH(CH.sub.2 CH.sub.3)--. 8. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 CH.sub.2 --. 9. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 CH(CH.sub.3)--. 10. A compound according to claim 1, wherein Q.sup.1 is --CH(CH.sub.3)CH.sub.2 --. 11. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 CH(CH.sub.2 CH.sub.3)--. 12. A compound according to claim 1, wherein Q.sup.1 is --CH(CH.sub.2 CH.sub.3)CH.sub.2 --. 13. A compound according to claim 1, wherein Q.sup.1 is --CH.dbd.CH--. 14. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 CH.sub.2 CH.sub.2 --. 15. A compound according to claim 1, wherein Q.sup.1 is --CH.dbd.CHCH.sub.2 --. 16. A compound according to claim 1, wherein Q.sup.1 is --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --. 17. A compound according to claim 1, wherein Q.sup.1 is --CH.dbd.CH.sub.2 CH.dbd.CH--. 18. A compound according to claim 1, wherein Q.sup.1 is selected from: --CH(CH.sub.3)CH.sub.2 CH.sub.2 CH.sub.2 --, 19. A compound according to claim 1, wherein R.sup.1 is hydrogen. 20. A compound according to claim 2, wherein R.sup.1 is hydrogen. 21. A compound according to claim 3, wherein R.sup.1 is hydrogen. 22. A compound according to claim 4, wherein R.sup.1 is hydrogen. 23. A compound according to claim 5, wherein R.sup.1 is hydrogen. 24. A compound according to claim 6, wherein R.sup.1 is hydrogen. 25. A compound according to claim 7, wherein R.sup.1 is hydrogen. 26. A compound according to claim 8, wherein R.sup.1 is hydrogen. 27. A compound according to claim 9, wherein R.sup.1 is hydrogen. 28. A compound according to claim 10, wherein R.sup.1 is hydrogen. 29. A compound according to claim 11, wherein R.sup.1 is hydrogen. 30. A compound according to claim 12, wherein R.sup.1 is hydrogen. 31. A compound according to claim 13, wherein R.sup.1 is hydrogen. 32. A compound according to claim 14, wherein R.sup.1 is hydrogen. 33. A compound according to claim 15, wherein R.sup.1 is hydrogen. 34. A compound according to claim 16, wherein R.sup.1 is hydrogen. 35. A compound according to claim 17, wherein R.sup.1 is hydrogen. 36. A compound according to claim 18, wherein R.sup.1 is hydrogen. 37. A compound of the following formula, and pharmaceutically acceptable salts thereof: ##STR407## 38. A compound of the following formula, and pharmaceutically acceptable salts thereof: ##STR408## 39. A compound according to claim 1, selected from compounds of the following formulae, and pharmaceutically acceptable salts and solvates thereof: ##STR409## ##STR410## 40. A composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier. 41. A composition comprising a compound according to claim 37, and a pharmaceutically acceptable carrier. 42. A composition comprising a compound according to claim 38, and a pharmaceutically acceptable carrier. 43. A composition comprising a compound according to claim 39, and a pharmaceutically acceptable carrier. 44. A method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound according to claim 1. 45. A method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound according to claim 37. 46. A method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound according to claim 38. 47. A method of inhibiting cell proliferation comprising contacting a cell with an effective amount of a compound according to claim 39. 48. A method of inhibiting HDAC comprising contacting a cell with an effective amount of a compound according to claim 1. 49. A method of inhibiting HDAC comprising contacting a cell with an effective amount of a compound according to claim 37. 50. A method of inhibiting HDAC comprising contacting a cell with an effective amount of a compound according to claim 38. 51. A method of inhibiting HDAC comprising contacting a cell with an effective amount of a compound according to claim 39. 52. A method of treating a proliferative condition in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 1. 53. A method of treating a proliferative condition in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 37. 54. A method of treating a proliferative condition in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 38. 55. A method of treating a proliferative condition in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 39. 56. A method of treating cancer in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 1. 57. A method of treating cancer in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 37. 58. A method of treating cancer in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 38. 59. A method of treating cancer in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 39. 60. A method of treating psoriasis in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 1. 61. A method of treating psoriasis in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 37. 62. A method of treating psoriasis in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 38. 63. A method of treating psoriasis in a patient comprising administering to said patient a therapeutically-effective amount of a compound according to claim 39.