Histone deacetylase inhibitors
Compounds of formula: (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: (I) wherein Q, V and W independently represent —N═ or —C═; B is a divalent radical selected from: (IIA), (IIB), (IIC), (IID), and (IIE). Wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; and -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical.
1. A compound of formula (IA) or a salt or N-oxide thereof:
wherein T is —S(═O) 2 —, —C(═O)— or —CH 2 —, and A is one of the following ring systems, optionally substituted:
2. A compound as claimed in claim 1 wherein ring A is optionally substituted quinolin-2-yl, or 1,3-dihydro-isoindol-2-yl.
3. A compound as claimed in claim 2 wherein optional substituents in ring A are selected from fluoro and chloro.
4. A compound as claimed in claim 1 which is selected from the group consisting of the following:
N-Hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, and
N-Hydroxy 2-{6-[(quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, and their N-oxides or salts, hydrates and solvates.
5. A pharmaceutical composition comprising a compound as claimed in claim 1 , together with a pharmaceutically acceptable carrier.
6. A pharmaceutical composition as claimed in claim 5 wherein the said compound is selected from the group consisting of the following:
N-Hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, and
N-Hydroxy 2-{6-[(quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide,
and their N-oxides or salts.