Hydroxamic acid compounds comprising a bicylic heteroaryl...

C - Chemistry – Metallurgy – 07 – D

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C07D 215/14 (2006.01) A61K 31/47 (2006.01) A61P 35/00 (2006.01) C07D 215/18 (2006.01) C07D 215/20 (2006.01) C07D 241/42 (2006.01) C07D 241/44 (2006.01) C07D 263/56 (2006.01) C07D 277/64 (2006.01)

Patent

CA 2516842

This invention pertains to certain carbamic acid compounds of the following formula (I), which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C1 7alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6- yl, then Q is unsubstituted at the .alpha.-position; and with the proviso that A is not benzimidazol-2-yl; 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 in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

L'invention concerne certains composés d'acide carbamique qui inhibent l'activité de HDAC (histone déacétylease) et qui sont représentés par la formule suivante, dans laquelle : A représente indépendamment un groupe hétéroaryle C¿9-10? bicyclique non substitué ou substitué (par exemple, quinolinyle; quinoxalinyle; benzoxazolyle; benzothiazolyle) ; Q représente un groupe acide de tête et représente indépendamment un groupe alkylène C¿1 7?, saturé ou non saturé, non substitué ou substitué présentant une longueur de squelette de 4 ou moins ; à la condition que si A représente benzothiazol-2-yle non substitué, Q représente un groupe non saturé ; et à la condition que si A représente quinolin-6-yle non substitué, Q n'est pas substitué en position ? ; et à la condition que A ne représente benzimidazol-2-yle. L'invention concerne également des sels pharmaceutiquement acceptables, des solvates, des amides, des esters, des éthers, des formes chimiquement protégées et des promédicaments de ces sels. L'invention concerne également des compositions pharmaceutiques comprenant ces composés ainsi que l'utilisation de ces composés et de ces compositions, in vitro et in vivo, pour inhiber HDAC et pour traiter des maladies médiées par HDAC, le cancer, les maladies proliférantes, le psoriasis, etc.

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