公开(公告)号：EP2029592A1

公开(公告)日：2009-03-04

申请号：EP07732559.5

申请日：2007-04-25

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

发明人： WOODHEAD, Steven, John ,  HAMLETT, Christopher ,  SORE, Hannah, Fiona ,  WALKER, David, Winter ,  VERDONK, Marinus, Leendert ,  COLLINS, Ian ,  CALDWELL, John ,  CHEUNG, Kwai-Ming ,  DA FONSECA MCHARDY, Tatiana, Faria

IPC分类号： C07D471/04 ,  C07D487/04 ,  A61K31/437 ,  A61K31/519 ,  A61P35/00

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

摘要： The invention provides compounds of the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein J1-J2 is CH=CH, N=CH, CH=N, HN-C(O) or CH2CO; T is N or CH and GP is as defined in the claims. The compounds have activity as inhibitors of PKA and PKB kinases and are useful in the treatment of cancers.

公开(公告)号：EP1919875A2

公开(公告)日：2008-05-14

申请号：EP06755590.4

申请日：2006-06-21

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

发明人： SORE, Hannah, Fiona ,  BOYLE, Robert, George ,  HAMLETT, Christopher ,  SAXTY, Gordon ,  VERDONK, Marinus, Leendert ,  WALKER, David, Winter ,  WOODHEAD, Steven, John ,  HOWARD, Steven

IPC分类号： C07D231/12 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D231/12 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof; wherein A is a saturated hydrocarbon linker group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; L1 is a bond or a linker selected from C1-C4 alkenylene, C1-C4 alkynylene, -CONR’, -NR’CO, -S-, -C(O)-, -C(NR11)-, -C(S)-, -N(R11)2, C(=CHR11), -SO- and -SO2-; or L1 together with t R16 forms an 8-12 membered fused bicyclic heteroaryl ring system; L3 is a bond or a linker selected from CONH and HNCO; provided that L1 and L3 cannot both be linkers simultaneously; and provided also that L1 and L3 cannot both be a bond simultaneously; R16 is an optionally substituted 5- to 12-membered monocyclic or bicyclic carbocyclic or heterocyclic ring; L2 is absent or is a linker selected from C]-C4 alkylene, Ci-C4 alkenylene, Ci-C4 alkynylene, -CONR’-, -NR’CO-, -O-, -S-, -C(O)-, C(=CHR11), C(S)-, -N(R11)2, C3-4 cycloalkanediyl, -SO- and -SO2-; R17 is absent or is C1-6 alkyl or an optionally substituted 5 to 12 membered carbocyclic or heterocyclic ring; provided that when R17 is absent, then L2 is also absent; and R2, R3, R4, R5, R11 and R’ are as defined in the claims. Compounds (I) modulate (PKA) and (PKB).

公开(公告)号：EP2013206A1

公开(公告)日：2009-01-14

申请号：EP07732554.6

申请日：2007-04-25

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

发明人： SAXTY, Gordon ,  VERDONK, Marinus, Leendert ,  CALDWELL, John ,  COLLINS, Ian ,  CHEUNG, Kwai-Ming ,  DA FONSECA MCHARDY, Tatiana, Faria

IPC分类号： C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D495/04

摘要： Compounds of the formula (I), and salts, solvates, tautomers and N-oxide thereof; wherein TG is selected from groups (1) and (2): wherein the asterisk (*) represents the point of attachment of the group E to the group X; Rla is an optionally substituted aryl or heteroaryl group; Rlb is hydrogen or a group Rla; X is an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 are heteroatoms selected from O, N and S; and A, E, R2, R3, R4, Q1 and Q2 are as defined in the claims; provided that when E is aryl or heteroaryl, then Q2 is other than a bond; and further provided that the moiety (a) is other than a group (BG1) or (BG2); wherein (BGl) and (BG2) are each optionally substituted; T is N or CRZ; J1-J2 is selected from N=C(RZ), (RZ)C=N, (RZ)N-C(O), (RZ)2C-C(O), N=N and (RZ)C=C(R6); J4 -J3 is a group N=C(RZ) or a group (RZ)N-CO; and RZ is hydrogen or a substituent. The compounds of the formula (I) have PKA and PKB kinase inhibiting activity and are useful in the treatment of cancers.

摘要翻译： 式（I）化合物及其盐，溶剂化物，互变异构体和N-氧化物; 其中TG选自组（1）和（2）：其中星号（*）表示基团E与基团X的连接点; R 1a是任选取代的芳基或杂芳基; R 1b是氢或基团R 1a; X是任选取代的具有8至12个环成员的双环杂环基团，其中至多5个是选自O，N和S的杂原子; 和A，E，R2，R3，R4，Q1和Q2如权利要求中所定义; 条件是当E是芳基或杂芳基时，则Q2不是键; 并进一步提供部分（a）不是基团（BG1）或（BG2）; 其中（BG1）和（BG2）各自任选被取代; T是N或CRZ; （RZ）C = N，（RZ）NC（O），（RZ）2C-C（O），N = N和（RZ）C = C（R 6） ）; J4-J3是基团N = C（RZ）或基团（RZ）N-CO; 并且RZ是氢或取代基。 式（I）化合物具有PKA和PKB激酶抑制活性并可用于治疗癌症。

公开(公告)号：EP1904451A1

公开(公告)日：2008-04-02

申请号：EP06755591.2

申请日：2006-06-21

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 ,  DOWNHAM, Robert ,  HAMLETT, Christopher ,  HOWARD, Steven ,  SORE, Hannah, Fiona ,  VERDONK, Marinus, Leendert ,  WALKER, David, Winter ,  LUKE, Richard, William, Arthur

IPC分类号： C07D231/12 ,  A61K31/415 ,  A61P37/02

CPC分类号： C07D231/12

摘要： The invention provides a compound of the formula (II): or a salt, solvate, tautomer or N-oxide thereof; wherein n is 0 or 1; one of Y1 and Y2 is CH and the other is selected from CH, CR8 and N; q is 0, 1 or 2 provided that q is 0 or 1 when Y1 or Y2 is CR8; R1 is an aryl or heteroaryl group of 5 to 10 ring members; R2a and R3a each are hydrogen, C1-4 hydrocarbyl or C1-4 acyl wherein the hydrocarbyl and acyl moieties are optionally substituted by fluorine, hydroxy, amino, methylamino, dimethylamino or methoxy; or NR2aR3a forms an imidazole group or a saturated monocyclic 4-7 membered heterocyclic group optionally containing a second heteroatom ring member selected from O and N; R18 is hydrogen or methyl; R19 is hydrogen or methyl; R24 is hydrogen or R24, R2a and the intervening nitrogen atom and carbon atoms together form an azetidine, pyrrolidine or piperidine ring; R25 is hydrogen or a C1-4 alkyl group wherein the C1-4 alkyl group is optionally substituted by hydroxy or amino provided that there are at least two carbon atoms between the hydroxy or amino group and the oxygen atom to which R25 is attached; and R4 and R5 each are hydrogen or a substituent as defined in the claims

公开(公告)号：EP1706385A1

公开(公告)日：2006-10-04

申请号：EP04806258.2

申请日：2004-12-23

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

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

IPC分类号： C07D231/12 ,  C07D413/10 ,  C07D401/10 ,  A61K31/415 ,  A61P37/02

CPC分类号： A61K31/415 ,  A61K9/0019 ,  A61K9/20 ,  A61K9/48 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D231/12 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D413/10

摘要： The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between Rl and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, 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 inker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; Rl is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

公开(公告)号：EP1706385B1

公开(公告)日：2010-10-06

申请号：EP04806258.2

申请日：2004-12-23

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

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

IPC分类号： C07D231/12 ,  C07D413/10 ,  C07D401/10 ,  A61K31/415 ,  A61P37/02

CPC分类号： A61K31/415 ,  A61K9/0019 ,  A61K9/20 ,  A61K9/48 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D231/12 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D413/10

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.