Title:
酵素阻害剤
Document Type and Number:
Japanese Patent JP5405820
Kind Code:
B2
Abstract:
Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers:
Wherein R 1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R 2 is the 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)NR 3 -, -C(=S)-NR 3 , -C(=NH)NR 3 or -S(=O) 2 NR 3 - wherein R 3 is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 )p- wherein m, 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 2 -Q 1 - or -Q 1 -X 2 - wherein X 2 is -O-, S- or NR A - wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl, and Q 1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, Alk 1 and Alk 2 independently represent optionally substituted divalent C 3 -C 7 , cycloalkyl radicals, or optionally substituted straight or branched, C 1 -C 6 alkylene, C 2 -C 6 alkenylene ,or C 2 -C 6 alkynylene radicals which may optionally contain or terminate in an ether (-O-), thioether (-S-) or amino (-NR A -) link wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl; X 1 represents a bond; -C(=O); or - S(=O) 2 -; -NR 4 C(=O)-, -C(=O)NR 4 -,-NR 4 C(=O)NR 5 -, -NR 4 S(=O) 2 -, or -S(=O) 2 NR 4 - wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R 1 R 2 NH-Y-L 1 -X 1 -[CH 2 ] z - and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent radical of formula -(CH 2 ) x - L 3 -Ar 1 -L 4 - wherein x is 0 or 1; L 3 is Z or L 2 or Z-L 2 wherein Z is a bond, -NR 3 -, -NR 3 C(=O)-, -C(=O)NR 3 -,-NR 4 C(=O)-NR 3 -, -C(=S)-NR 3 , -C(=N)-NR 3 -NR 3 S(=O) 2 -, or -S(=O) 2 NR 3 - wherein R 3 is hydrogen or C 1 -C 6 alkyl; - C(=O); or -S(=O) 2 -; and L 2 is a bond or an optionally substituted divalent C 1 -C 3 alkylene radical; Ar 1 is a divalent phenyl radical or a divalent mono-, or bi-cyclic heteroaryl radical having 5 to 13 ring members; and L 4 is a bond or optionally substituted -CH 2 - or -CH=CH-.
More Like This:
Inventors:
Davidson, Alan, Hornsby
Patel, Sanjay, Lateral
Massey, Francesca, Anne
Davis, Stephen, John
Drummond, Alan, Hastings
Moffat, David, Festus, Charles
Baker, kenneth, william, john
Donald, Alistair, David, Graham
Patel, Sanjay, Lateral
Massey, Francesca, Anne
Davis, Stephen, John
Drummond, Alan, Hastings
Moffat, David, Festus, Charles
Baker, kenneth, william, john
Donald, Alistair, David, Graham
Application Number:
JP2008509500A
Publication Date:
February 05, 2014
Filing Date:
May 04, 2006
Export Citation:
Assignee:
CHROMA THERAPEUTICS LTD
International Classes:
C07C259/06; A61K31/198; A61K31/223; A61K31/381; A61K31/401; A61K31/405; A61K31/437; A61K31/44; A61K31/472; A61K31/495; A61K31/63; A61P3/00; A61P3/10; A61P7/00; A61P19/02; A61P25/00; A61P25/28; A61P29/00; A61P35/00; A61P37/06; A61P43/00; C07C275/24; C07C311/46; C07D207/16; C07D207/416; C07D209/42; C07D213/40; C07D213/75; C07D217/02; C07D217/22; C07D295/185; C07D333/70; C07D471/04; C07D207/40
Domestic Patent References:
| JP2004516325A | ||||
| JP2004509105A |
Foreign References:
| WO2003066579A2 | ||||
| WO2004113336A1 | ||||
| WO2005034880A2 | ||||
| WO2005037272A1 | ||||
| EP0177366A1 | ||||
| GB2279345A |
Other References:
INAOKA,Y. and NARUTO,S.,Propioxatins A and B, new enkephalinase B inhibitors. IV. Characterization of the active site of the enzyme using synthetic propioxatin analogs,JOURNAL OF BIOCHEMISTRY,日本,JAPANESE BIOCHEMICAL SOCIETY,1988年11月,Vol.104, No.5,p.706-711
TAMAKI,K. et al.,Synthesis and structure-active relationships of gelatinase inhibitors derived from matlystatins,CHEMICAL AND PHARMACEUTICAL BULLETIN,日本,PHARMACEUTICAL SOCIETY OF JAPAN,1995年11月,Vol.43, No.11,p.1883-1893
WOLZ,R.L.,A kinetic comparison of the homologous proteases astacin and meprin A,ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,1994年 4月,Vol.310, No.1,p.144-151
TAMAKI,K. et al.,Synthesis and structure-active relationships of gelatinase inhibitors derived from matlystatins,CHEMICAL AND PHARMACEUTICAL BULLETIN,日本,PHARMACEUTICAL SOCIETY OF JAPAN,1995年11月,Vol.43, No.11,p.1883-1893
WOLZ,R.L.,A kinetic comparison of the homologous proteases astacin and meprin A,ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,1994年 4月,Vol.310, No.1,p.144-151
Attorney, Agent or Firm:
Shintaro Nogawa