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HYDROXAMIC ACID DERVICATIVES AS INHIBITORS OF HDAC ENZYMATIC ACTIVITY
专利权人:
发明人:
申请号:
EP06726980.3
公开号:
EP1877366B1
申请日:
2006.05.04
申请国别(地区):
EP
年份:
2012
代理人:
摘要:
Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers: formula (I) wherein Y1 is a bond, -(C=O)-, -S(O2)-, -C(=O)O-, -OC(=O)-, -(C=O)NR3, -NR3(C=O)-, -S(O2)NR3-, -NR3S(O2)-, or -NR3(C=O)NR5-, wherein R3 and R5 are independently hydrogen or optionally substituted (C1-C6)alkyl, L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n, p, AIk1, AIk2 and Q are as defined in the claims z is O or 1 A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system -[Linker]- represents a divalent linker radical R is a radical of formula (X) or (Y) wherein R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group R4 is hydrogen or optionally substituted C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, heteroaryl(C1-C6 alkyl)-, -(C=O)R3, -(C=O)OR3, or -(C=O)NR3 wherein R3 is hydrogen or optionally substituted (C1-C6)alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, or heteroary(C1-C6 alkyl)- R41 is hydrogen or optionally substituted C1-C6 alkyl and B is a monocyclic heterocyclic ring of 5 or 6 ring atoms wherein R1 is linked to a ring carbon adjacent the ring nitrogen shown, and ring B is optionally fused to a second carbocyclic or heterocyclic ring of 5 or 6 ring atoms in which case the bond shown intersected by a wavy line may be from a ring atom in said second ring.Les composés de formule (I) sont des inhibiteurs de lactivité de lhistone désacétylase et sont utiles dans le traitement, par exemple, de cancers : formule (I) dans laquelle Y1 est une liaison, -(C=O)-, -S(O2)-, -C(=O)O-, -OC(=O)-, -(C=O)NR3, -NR3(C=O)-, -S(O2)NR3-, -NR3S(O2)- ou -NR3(C=O)NR5-, R3 et R5 étant indépendamment un hydrogène ou un alkyle en C1-C6 éventuellement substitué L1 est un radical divalent de formule -(Alk1)m(Q)n(Alk2)p- dans laquel
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