公开(公告)号：WO2006038001A1

公开(公告)日：2006-04-13

申请号：PCT/GB2005/003827

申请日：2005-10-04

Applicant: CELLTECH R & D LIMITED ,  RATCLIFFE, Andrew, James ,  ALAM, Mahbub ,  BEEVERS, Rebekah, Elisabeth ,  DAVENPORT, Richard, John ,  DAVIES, Natasha ,  HAUGHAN, Alan, Findlay ,  JONES, Mark, William ,  LOWE, Christopher ,  PERRY, Benjamin, Garfield ,  PHILLIPS, David, Jonathan ,  PITT, William, Ross ,  SHARPE, Andrew

Inventor： RATCLIFFE, Andrew, James ,  ALAM, Mahbub ,  BEEVERS, Rebekah, Elisabeth ,  DAVENPORT, Richard, John ,  DAVIES, Natasha ,  HAUGHAN, Alan, Findlay ,  JONES, Mark, William ,  LOWE, Christopher ,  PERRY, Benjamin, Garfield ,  PHILLIPS, David, Jonathan ,  PITT, William, Ross ,  SHARPE, Andrew

IPC: C07D401/14

CPC classification number: C07D409/14 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: A compound of formula (I) or a pharmaceutically acceptable salt, solvate or N-­oxide thereof: wherein A represents a pyrrole, pyrazole, imidazole or triazole ring; B represents a benzene, pyridine or pyrimidine ring; M represents the residue of an azetidine, pyrrolidine or piperidine ring; E represents a covalent bond or an optionally substituted straight or branched alkylene chain containing from 1 to 4 carbon atoms; Z represents hydrogen, -CORa, -C0 2 R b , -CONK c R d , -CONR c OR b , -COCO 2 R b , - COCONR c R d , -COCH2NR c R d , -COCH2NR c CONK c R d , COCH2NR c CO 2 R b , -NR c COR a , - NR c CO2R b , -NR c CONR c R d , -S0 2 R e , -SO 2 NR c R d or -SO2NR c C0 2 R b ; or Z represents an optionally substituted phenyl, heteroaryl or C 3-7 heterocycloalkyl group; R 1 and R 2 independently represent hydrogen, halogen, cyano, nitro, C 1-6 alkyl, trifluoromethyl, hydroxy, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C 1-6 alkylsulphonyl, amino, C 1-6 alkylamino, di(C 1-6 )alkylamino, aminocarbonyl or C 2-6 alkoxycarbonyl; R 3 represents hydrogen, C 1-6 alkyl, -CH2CONR c R d or -SO 2 R e ; R 4 represents hydrogen, C 1-6 alkoxy, oxo, -CO2R b or -CONK c R d . The compounds of the present invention are potent inhibitors of JNK.

Abstract translation: 式（I）化合物或其药学上可接受的盐，溶剂合物或N-氧化物：其中A表示吡咯，吡唑，咪唑或三唑环; B代表苯，吡啶或嘧啶环; M表示氮杂环丁烷，吡咯烷或哌啶环的残基; E表示共价键或含有1至4个碳原子的任选取代的直链或支链亚烷基链; Z表示氢，-CORa，-C0

公开(公告)号：WO2004022554A1

公开(公告)日：2004-03-18

申请号：PCT/GB2003/003878

申请日：2003-09-05

Applicant: CELLTECH R & D LIMITED ,  HAUGHAN, Alan, Findlay ,  BUCKLEY, George, Martin ,  DAVIES, Natasha ,  DYKE, Hazel, Joan ,  HANNAH, Duncan, Robert ,  MORGAN, Trevor ,  RICHARD, Marianna, Dilani ,  SHARPE, Andrew ,  WILLIAMS, Sophie, Caroline

Inventor： HAUGHAN, Alan, Findlay ,  BUCKLEY, George, Martin ,  DAVIES, Natasha ,  DYKE, Hazel, Joan ,  HANNAH, Duncan, Robert ,  MORGAN, Trevor ,  RICHARD, Marianna, Dilani ,  SHARPE, Andrew ,  WILLIAMS, Sophie, Caroline

IPC: C07D413/04

CPC classification number: C07D413/04 ,  C07D239/70 ,  C07D471/10 ,  C07D487/10 ,  C07D491/10

Abstract: A compound of formula (1), wherein: X is an oxygen or sulfur atom; R 1 is an aliphatic, cycloaliphatic or cycloalkyl-alkyl- group; R 2 is an optionally substituted heteroaromatic group or a -CN group; R 3 is a group -(Alk 1 ) m L 1 (AIk 2 ) n R 4 in which m and n, which may be the same or different, is each zero or the integer 1, Alk 1 and AIk 2 , which may be the same or different, is each an optionally substituted aliphatic or heteroaliphatic chain, L 1 is a covalent bond or a linker atom or group and R 4 is a hydrogen atom or an optionally substituted cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; A is an optionally substituted cycloaliphatic or heterocycloaliphatic group optionally fused to an optionally substituted aryl or heteroaryl group; R 5 , which may be attached to any available C or N atom present in the cycloaliphatic or heterocycloaliphatic, or where fused, aryl or heteroaryl group, is a group -(AIk 3 ) t L 2 (AIk 4 ) v R 6 in which t and v, which may be the same or different, is each zero or the integer 1, Alk 3 and AIk 4 , which may be the same or different, is each an optionally substituted aliphatic or heteroaliphatic chain, L 2 is a covalent bond or a linker atom or group and R 6 is a hydrogen or halogen atom or a -CN group or an optionally substituted cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates, tautomers, isomers or N-oxides thereof. The compounds of the present invention are potent inhibitors of IMPDH.

Abstract translation: 式（1）的化合物，其中：X是氧或硫原子; R 1是脂族，脂环族或环烷基 - 烷基; R 2是任选取代的杂芳基或-CN基; R 3是基团 - （Alk 1）mL -1（Alk 2）n R 4，其中m和n可以相同或不同，分别为零或整数1， Alk 1和Alk 2可以相同或不同，各自为任选取代的脂族或杂脂族链，L 1为共价键或连接原子或基团，R 4为氢 原子或任选取代的脂环族，杂脂族，芳族或杂芳族基团; A是任选地与任选取代的芳基或杂芳基稠合的任选取代的脂环族或杂环脂族基; R 5可以连接在存在于脂环族或杂环脂族基中的任何可用的C或N原子上，或者其中稠合的，芳基或杂芳基是基团 - （Alk 3）tL 2（Alk <4） >）vR <6>其中可以相同或不同的t和v各自为零或整数1，Alk 3和Alk 4可以相同或不同，各自为任选地 取代的脂族或杂脂族链，L 2是共价键或连接原子或基团，R 6是氢或卤素原子或-CN基团或任选取代的脂环族，杂脂族，芳族或杂芳族基团; 及其盐，溶剂合物，水合物，互变异构体，异构体或N-氧化物。 本发明的化合物是IMPDH的有效抑制剂。

公开(公告)号：WO2003035066A1

公开(公告)日：2003-05-01

申请号：PCT/GB2002/004754

申请日：2002-10-22

Applicant: CELLTECH R & D LIMITED ,  HAUGHAN, Alan, Findlay ,  DYKE, Hazel, Joan ,  BUCKLEY, George, Martin ,  DAVIES, Natasha ,  HANNAH, Duncan, Robert ,  RICHARD, Marianna, Dilani ,  SHARPE, Andrew ,  WILLIAMS, Sophie, Caroline

Inventor： HAUGHAN, Alan, Findlay ,  DYKE, Hazel, Joan ,  BUCKLEY, George, Martin ,  DAVIES, Natasha ,  HANNAH, Duncan, Robert ,  RICHARD, Marianna, Dilani ,  SHARPE, Andrew ,  WILLIAMS, Sophie, Caroline

IPC: A61K31/422

CPC classification number: C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D413/04 ,  C07D413/14

Abstract: Quinolone derivatives of formula (1) are described; wherein: X is an O or S atom; R 1 is an aliphatic, cycloaliphatic, or cycloalkyl-alkyl-group; R 2 is a -CN group or an optionally substituted heteroaromatic group; R 3 is a hydrogen atom or an alkyl, -CN, -CO 2 H, -CO 2 R 6 or -CONR 7 R 8 group; R 4 is a chain -Alk 1 -L 1 -Alk 2 -R 9 ; R 5 is a hydrogen atom or an alkyl group; or NR 4 R 5 forms an optionaly substituted heterocycloaliphatic ring optionally fused to an optionally substituted monocylcic C 6-12 aromatic group or an optionally substituted monocyclic C 1-9 heteroaromatic group; and the salts, solvates, hydrates, tautomers, isomers or N -oxides thereof. The compounds are potent inhibitors of IMPDH and are of use as immunosuppressants, anti-cancer agents, anti-inflammatory agents, antipsoriatic and anti-viral agents.

Abstract translation: 描述了式（1）的喹诺酮衍生物; 其中：X是O或S原子; R 1是脂族，脂环族或环烷基 - 烷基; R 2是-CN基团或任选取代的杂芳族基团; R 3是氢原子或烷基，-CN，-CO 2 S，H，-CO 2 s，R 6，sp >或-CONR R 8 组; R 4 是链-Alk -L 1 -Alk SP>; R 5是氢原子或烷基; 或任选地与任选取代的单环C 6-12芳族基团或任选取代的单环的稠合的任选的杂环脂族环 杂芳族基团; 及其盐，溶剂合物，水合物，互变异构体，异构体或其N-氧化物。 这些化合物是IMPDH的有效抑制剂，可用作免疫抑制剂，抗癌剂，抗炎剂，抗牛皮癣和抗病毒剂。