DAVIDSON, ALAN HORNSBY,PATEL, SANJAY RATILAL,MAZZEI, FRANCESCA ANN,DAVIES, STEPHEN JOHN,DRUMMOND, ALAN HASTINGS,MOFFAT, DAVID FESTUS CHARLES,BAKER, KENNETH WILLIAM JOHN,DONALD, ALISTAIR DAVID GRAHAM
申请号：
CA2599411
公开号：
CA2599411C
申请日:
2006.05.04
申请国别(地区):
CA
年份:
2013
代理人:
摘要：
Compounds of formula (I) are inhibitors of histone deacetylase activity, andare useful in the treatment of, for example, cancers, wherein R1 is acarboxylic acid group (-COOH), or an ester group which is hydrolysable by oneor more intracellular carboxyesterase enzymes to a carboxylic acid group； R2isthe side chain of a natural or non-natural alpha amino acid； Y is a bond, -C(=O)-, -S(=O)2-, -C(=O)O-, -C(O)NR3-, -C(=S)-NR3 , -C(=NH)NR3 or -S(=O)2NR3-wherein R3 is hydrogen or optionally substituted C1-C6 alkyl； L1 is a divalentradical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0or 1 , Q is (i) an optionally substituted divalent mono- or bicycliccarbocyclic or heterocyclic radical having 5 - 13 ring members, or (ii), inthe case where both m and p are 0, a divalent radical of formula -X2-Q1- or -Q1-X2- wherein X2 is -O-, S- or NRA- wherein RA is hydrogen or optionallysubstituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- orbicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, AIk1and AIk2 independently represent optionally substituted divalent C3-C7cycloalkyl radicals, or optionally substituted straight or branched, C1-C6alkylene, C2-C6 alkenylene ,or C2-C6 alkynylene radicals which may optionallycontain or terminate in an ether (-O-), thioether (-S-) or amino (-NRA-) linkwherein RA is hydrogen or optionally substituted C1-C3 alkyl； X1 represents abond； -C(=O)； or -S(=O)2-； -NR4C(=O)-, -C(=O)NR4-, -NR4C(=O)NR5- , -NR4S(=O)2-, or -S(=O)2NR4-wherein R4 and R5 are independently hydrogen or optionallysubstituted C1-C6 alkyl； z is 0 or 1 ； A represents an optionally substitutedmono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein theradicals R1R2NH-Y-L1-X1-[CH2]Z- and HONHCO-[LINKER]- are attached differentring atoms； and -[Linker]- represents a divalent linker radical linking a ringatom in A with the hydroxamic acid group CONHOH, the le
