Carbamic acid compounds comprising an ether linkage as hdac...

C - Chemistry – Metallurgy – 07 – C

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C07C 323/60 (2006.01) A61P 17/06 (2006.01) A61P 35/00 (2006.01) C07C 259/06 (2006.01)

Patent

CA 2423970

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula(I) wherein: A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is an amide linkage selected from: -NR1C(=O)- and -C(=O)NR1-; R1 is an amido substituent; X is an ether heteroatom, and is -O- or -S-; and, R2 and R3 are each independently an ether 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.

L'invention concerne certains composés d'acide carbamique, actifs, inhibant l'activité de HDAC (histone désacétylase) et possédant la formule suivante (I) dans laquelle A représente un groupe aryle, Q?1¿ représente une liaison covalente ou un groupe leader aryle, J représente une liaison amide choisie entre -NR?1¿C(=O)- et -C(=O)NR?1¿-, R¿1? représente un substituant amido, X représente un hétéroatome d'éther et représente -O- ou -S-, et R?2¿ et R?3¿ représentent chacun indépendamment un groupe éther. L'invention concerne également des sels, solvates, amides, esters, éthers, formes chimiquement protégées, et promédicaments de ces composés, et elle concerne encore des compositions pharmaceutiques comprenant de tels composés, ainsi que l'utilisation de ces composés et compositions, à la fois in vitro et in vivo, pour inhiber HDAC et, par exemple, pour inhiber des désordres prolifératifs, tels que le cancer et le psoriasis.

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