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：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：EP1812003A1

公开(公告)日：2007-08-01

申请号：EP05796842.2

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 ,  VERDONK, Marinus, Leendert ,  WOODHEAD, Steven, John ,  WYATT, Paul, Graham ,  SORE, Hannah, Fiona ,  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 ,  C07D473/00

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

摘要： The invention provides a compound for use in the prophylaxis or treatment of a disease state or condition mediated by protein kinase B, the compound having the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein T is N or 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); A is an optionally substituted saturated C1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH2, O, S or NH and G is a C1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R1 is hydrogen or an aryl or heteroaryl group; R2 and R3 are each hydrogen, optionally substituted C1-4 hydrocarbyl or optionally substituted C1-4 acyl; or NR2R3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR2R3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C1-4 alkyl; or NR2R3 and the adjacent carbon atom of linker group A together form a cyano group; or R1, A and NR2R3 together form a cyano group; and R4, R5, R6, R7 and R8 are each independently selected from hydrogen and various substituents as defined in the claims.