公开(公告)号：EP1812004B1

公开(公告)日：2011-06-22

申请号：EP05797685.4

申请日：2005-10-25

申请人： Astex Therapeutics Limited ,  The Institute of Cancer Research: Royal Cancer Hospital ,  Cancer Research Technology Limited

发明人： BERDINI, Valerio ,  BOYLE, Robert George ,  SAXTY, Gordon ,  WALKER, David Winter ,  WOODHEAD, Steven John ,  WYATT, Paul Graham ,  CALDWELL, John ,  COLLINS, Ian ,  DA FONSECA, Tatiana Faria ,  DONALD, Alastair

IPC分类号： A61K31/52 ,  A61K31/519 ,  C07D473/34 ,  A61K31/437 ,  C07D471/04 ,  C07D487/04

CPC分类号： C07D471/04 ,  A61K31/4545 ,  A61K31/519 ,  A61K31/52 ,  A61K31/522 ,  C07D473/34 ,  C07D487/04

摘要： The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR5; Jl-J2 is N=C(R6), (R7)C=N, (R8)N-C(O), (R8)2C-C(O), N=N or (R7)C=C(R6); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q1 is a bond or a saturated C1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRq or NRqCO where Rq is hydrogen or methyl, or Rq is a C1-4 alkylene chain linked to R1 or a carbon atom of Q1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q2 is other than a bond; G is hydrogen, NR2R3, OH or SH provided that when E is aryl or heteroaryl and Q2 is a bond, then G is hydrogen; R1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R1 is hydrogen and G is NR2R3, then Q2 is a bond; and R2, R3, R4, R6 and R8 are as defined in the claims.

公开(公告)号：EP2125805A1

公开(公告)日：2009-12-02

申请号：EP07848736.0

申请日：2007-12-20

申请人： Astex Therapeutics Limited ,  The Institute of Cancer Research: Royal Cancer Hospital ,  Cancer Research Technology Limited

发明人： WOODHEAD, Steven John ,  FREDERICKSON, Martyn ,  HAMLETT, Christopher ,  WOODHEAD, Andrew James ,  VERDONK, Marinus Leendert ,  SORE, Hannah Fiona ,  WALKER, David Winter ,  BLURTON, Peter ,  COLLINS, Ian ,  CHEUNG, Kwai Ming ,  CALDWELL, John ,  DA FONSECA McHARDY, Tatiana Faria ,  LUKE, Richard William Arthur ,  MATUSIAK, Zbigniew Stanley ,  LEACH, Andrew ,  MORRIS, Jeffrey James

IPC分类号： C07D471/04 ,  C07D473/34 ,  C07D487/04 ,  C07D519/00 ,  A61K31/437 ,  A61K31/52 ,  A61P35/00

CPC分类号： C07D487/04 ,  C07D471/04 ,  C07D473/34 ,  C07D519/00

摘要： The invention provides PKA and PKB kinase-inhibiting compounds of the formula (I); or salts, solvates, tautomers or N-oxides thereof, wherein E is a five membered heteroaryl ring containing 1, 2, 3 or 4 heteroatoms selected from O, N and S provided that no more than 1 heteroatom may be other than N; q and r are each is 0 or 1; provided that q+r is 1 or 2; T is N or a group CR5; J1-J2 is N=C(R6), (R7)C=N, (R8)N- C(O), (R8)2C-C(O), N=N or (R7)C=C(R6); Q3 is a bond or a saturated C1-3 hydrocarbon linker group optionally substituted by fluorine and hydroxy; G is NR2R3, CN or OH; m and n are each 0 or 1, provided that m+n is 1 or 2, and provided also that m or n are each 0 when the adjacent ring member of ring E is S or O; R1a and R1b are the same or different and each is hydrogen or a substituent R10; or R1a and R1b together with the carbon atoms or heteroatoms to which they are attached form a 5 or 6-membered aryl or heteroaryl ring, wherein the aryl or heteroaryl rings are optionally substituted by one or more substituents R10; and R2, R3, R4, R5, R7, R6, R8, and R10 are as defined in the claims.

公开(公告)号：EP1812004A1

公开(公告)日：2007-08-01

申请号：EP05797685.4

申请日：2005-10-25

申请人： Astex Therapeutics Limited ,  THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL ,  Cancer Research Technology Limited

发明人： BERDINI, Valerio ,  BOYLE, Robert George ,  SAXTY, Gordon ,  WALKER, David Winter ,  WOODHEAD, Steven John ,  WYATT, Paul Graham ,  CALDWELL, John ,  COLLINS, Ian ,  DA FONSECA, Tatiana Faria ,  DONALD, Alastair

IPC分类号： A61K31/52 ,  A61K31/519 ,  C07D473/34 ,  A61K31/437 ,  C07D471/04 ,  C07D487/04

CPC分类号： C07D471/04 ,  A61K31/4545 ,  A61K31/519 ,  A61K31/52 ,  A61K31/522 ,  C07D473/34 ,  C07D487/04

摘要： The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR5; Jl-J2 is N=C(R6), (R7)C=N, (R8)N-C(O), (R8)2C-C(O), N=N or (R7)C=C(R6); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q1 is a bond or a saturated C1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRq or NRqCO where Rq is hydrogen or methyl, or Rq is a C1-4 alkylene chain linked to R1 or a carbon atom of Q1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q2 is other than a bond; G is hydrogen, NR2R3, OH or SH provided that when E is aryl or heteroaryl and Q2 is a bond, then G is hydrogen; R1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R1 is hydrogen and G is NR2R3, then Q2 is a bond; and R2, R3, R4, R6 and R8 are as defined in the claims.

公开(公告)号：EP2125820A1

公开(公告)日：2009-12-02

申请号：EP07848737.8

申请日：2007-12-20

申请人： Astex Therapeutics Limited ,  The Institute of Cancer Research: Royal Cancer Hospital ,  Cancer Research Campaign Technology Limited ,  AstraZeneca AB

发明人： WOODHEAD, Steven John ,  HAMLETT, Christopher ,  VERDONK, Marinus Leendert ,  SORE, Hannah Fiona ,  WALKER, David Winter ,  COLLINS, Ian ,  CALDWELL, John ,  DA FONSECA McHARDY, Tatiana Faria ,  LUKE, Richard William Arthur ,  MATUSIAK, Zbigniew Stanley ,  CARR, Gregory Richard ,  MORRIS, Jeffrey James ,  CHEUNG, Kwai Ming

IPC分类号： C07D487/04 ,  C07D473/34 ,  C07D471/04 ,  A61K31/519 ,  A61P35/00

CPC分类号： C07D473/34 ,  C07D487/04

摘要： The invention provides compounds of the formula (I) having PKA and PKB kinase inhibiting compounds of the formula (I): GP 1 J T 2 J N 4 R N H (I) or salts, solvates, tautomers or N-oxides thereof, wherein (1) GP is a group GP1: HET 2a a Q G (HNCO)f 7 (R )x N * (GP1) (2) GP is a group GP2: 10 (R )r O 2a a QG (CH2)w N V H N * (GP2) wherein HET is a monocyclic or bicyclic heterocyclic group containing up to 4 heteroatom ring members; the ring V is a monocyclic or bicyclic heteroaryl group of 5 to 10 ring members; and J1, J2, R4, R7, R10, Q2a, Ga, x, w and f are as defined in the claims

摘要翻译： （I）的化合物或其盐，溶剂合物，互变异构体或N-氧化物，其中（1）具有式 GP是基团GP1：HET 2a a QG（HNCO）f 7（R）x N *（GP1）（2）GP是基团GP2：10（R）r O 2a a QG（CH2）w NVHN *（GP2 ）其中HET是含有至多4个杂原子环成员的单环或双环杂环基团; 环V是5至10个环成员的单环或双环杂芳基; 和J1，J2，R4，R7，R10，Q2a，Ga，x，w和f如权利要求中所定义

公开(公告)号：EP1814552A2

公开(公告)日：2007-08-08

申请号：EP05801609.8

申请日：2005-11-09

申请人： Astex Therapeutics Limited ,  The Institute of Cancer Research : The Royal Cancer Hospital ,  Cancer Research Technology Limited

发明人： BERDINI, Valerio ,  BOYLE, Robert George ,  SAXTY, Gordon ,  VERDONK, Marinus Leendert ,  WOODHEAD, Steven John ,  WYATT, Paul Graham ,  SORE, Hannah Fiona ,  WALKER, David Winter ,  CALDWELL, John ,  COLLINS, Ian

IPC分类号： A61K31/505 ,  A61P35/00 ,  C07D239/88 ,  C07D401/12 ,  C07D401/04 ,  C07D401/06 ,  C07D403/12

CPC分类号： C07D403/12 ,  A61K31/505 ,  C07D239/88 ,  C07D239/91 ,  C07D239/96 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04

摘要： The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof for use in the treatment or prophylaxis of a disease state or condition mediated by protein kinase A and/or protein kinase B, wherein the ring Q is a benzene ring; J2-J1 is N=CR7 or R1aN-CO; G is OH or NR5R6; E is CONR7, NR7CO, C(R8)=C(R8) or (X)m(CR8R8a)n where X is O, S or NR7; provided that when J2-J1 is R1aN-CO, E is other than NR7CO; m and n are each 0 or 1, where m + n = 1 or 2; A is a bond and R4 and R4a are absent, or A is a saturated optionally group having a maximum chain length of 5 atoms extending between E and G, one carbon atom in the linker group A being optionally replaced by O or N.