Donald, Alistair David Graham,Mazzei, Francesca Ann,Drummond, Alan Hastings,Baker, Kenneth William John,Davidson, Alan Hornsby,Davies, Stephen John,Moffat, David Festus Charles,Patel, Sanjay Ratilal
申请号：
AU2006243065
公开号：
AU2006243065B2
申请日:
2006.05.04
申请国别(地区):
AU
年份:
2012
代理人:
摘要：
Compounds of formula (I) are inhibitors of histone deacetylase activity, and areuseful in the treatment of, for example, cancers, wherein Ris a carboxylicacid group (-COOH), or an ester group which is hydrolysable by one or more intracellularcarboxyesterase enzymes to a carboxylic acid group； Ris the sidechain of a natural or non-natural alpha amino acid； Y is a bond, -C(=O)-, -S(=O)-,-C(=O)O-, -C(O)NR-, -C(=S)-NR , -C(=NH)NRor -S(=O)NR- wherein R is hydrogen or optionallysubstituted C-C alkyl； L is a divalent radicalof formula -(Alk)(Q)(Alk)- whereinm, n and p are independently 0 or 1 , Q is (i) an optionally substituted divalent mono-or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, or(ii), in the case where both m and p are 0, a divalent radical of formula -X-Q- or-Q-X- wherein X is -O-, S- or NR- whereinR is hydrogen or optionally substituted C-C alkyl,and Q is an optionally substituted divalent mono- or bicyclic carbocyclicor heterocyclic radical having 5 - 13 ring members, AIk and AIkindependently represent optionally substituted divalent C-Ccycloalkyl radicals, or optionally substituted straight or branched, C-Calkylene, C-C alkenylene ,or C-Calkynylene radicals which may optionally contain or terminate in an ether (-O-),thioether (-S-) or amino (-NR-) link wherein R is hydrogenor optionally substituted C-C alkyl； X representsa bond； -C(=O)； or -S(=O)-； -NRC(=O)-, -C(=O)NR-,-NRC(=O)NR- , -NRS(=O)-, or -S(=O)NR-whereinR and R are independently hydrogen or optionally substitutedC-C alkyl； z is 0 or 1 ； A represents an optionally substitutedmono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein theradicals RRNH-Y-L-X-[CH]- andHONHCO-[LINKER]- are attached different ring atoms； and -[Linker]- represents adivalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH,the length o
