公开(公告)号：US20100210617A1

公开(公告)日：2010-08-19

申请号：US11993835

申请日：2006-06-21

申请人： Steven John Woodhead ,  Robert Downham ,  Christopher Hamlett ,  Steven Howard ,  Hannah Fiona Sore ,  Marinus Leendert Verdonk ,  David Winter Walker ,  Richard William Arthur Luke

发明人： Steven John Woodhead ,  Robert Downham ,  Christopher Hamlett ,  Steven Howard ,  Hannah Fiona Sore ,  Marinus Leendert Verdonk ,  David Winter Walker ,  Richard William Arthur Luke

IPC分类号： A61K31/4155 ,  C07D231/12 ,  C07D403/10 ,  C07D413/10 ,  C07D413/14 ,  C07D401/10 ,  A61K31/415 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/497 ,  A61K31/454 ,  A61P35/00

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 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

摘要翻译： 本发明提供式（II）化合物或其盐，溶剂合物，互变异构体或N-氧化物; 其中n为0或1; Y1和Y2之一是CH，另一个选自CH，CR8和N; q为0,1或2，条件是当Y1或Y2为CR8时q为0或1; R 10芳环或5至10个环成员的杂芳基; R2a和R3a各自为氢，C1-4烃基或C1-4酰基，其中烃基和酰基部分任选被氟，羟基，氨基，甲基氨基，二甲基氨基或甲氧基取代; 或NR2aR3a形成任选含有选自O和N的第二杂原子环成员的咪唑基或饱和单环4-7元杂环基; R18是氢或甲基; R 19是氢或甲基; R 24是氢或R 24，R 2a，并且插入的氮原子和碳原子一起形成氮杂环丁烷，吡咯烷或哌啶环; R 25是氢或C 1-4烷基，其中C 1-4烷基任选被羟基或氨基取代，条件是羟基或氨基与R 25所连接的氧原子之间至少有两个碳原子; 且R 4和R 5各自为氢或如权利要求中所定义的取代基

公开(公告)号：US20100093748A1

公开(公告)日：2010-04-15

申请号：US12520303

申请日：2007-12-21

申请人： Steven John Woodhead ,  Martyn Frederickson ,  Christopher Hamlett ,  Andrew James Woodhead ,  Marinus Leendert Verdonk ,  Hannah Fiona Sore ,  David Winter Walker ,  Peter Blurton ,  Ian Collins ,  Kwai Ming Cheung ,  John Caldwell ,  Tatiana Faria Da Fonseca McHardy ,  Richard William Arthur Luke ,  Zbigniew Stanley Matusiak ,  Andrew Leach ,  Jeffrey James Morris

发明人： Steven John Woodhead ,  Martyn Frederickson ,  Christopher Hamlett ,  Andrew James Woodhead ,  Marinus Leendert Verdonk ,  Hannah Fiona Sore ,  David Winter Walker ,  Peter Blurton ,  Ian Collins ,  Kwai Ming Cheung ,  John Caldwell ,  Tatiana Faria Da Fonseca McHardy ,  Richard William Arthur Luke ,  Zbigniew Stanley Matusiak ,  Andrew Leach ,  Jeffrey James Morris

IPC分类号： A61K31/497 ,  C07D487/04 ,  A61K31/519 ,  C07D471/04 ,  A61K31/437

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.

摘要翻译： 本发明提供式（I）的PKA和PKB激酶抑制化合物：或其盐，溶剂合物，互变异构体或N-氧化物，其中E是含有1,2,3或4个选自O， N和S的条件是不超过1个杂原子可以不是N; q和r各自为0或1; q + r为1或2; T为N或CR5基团; J1-J2是N = C（R6），（R7）C = N，（R8）N-C（O），（R8）2C-C（O），N = N或（R7）C = C ）; Q3是任选被氟和羟基取代的键或饱和C 1-3烃连接基团; G为NR2R3，CN或OH; m和n各自为0或1，条件是m + n为1或2，并且当环E的相邻环构件为S或O时，m或n各自为0; R1a和R1b相同或不同，各自为氢或取代基R10; 或R 1a和R 1b与它们所连接的碳原子或杂原子一起形成5或6元芳基或杂芳基环，其中芳基或杂芳基环任选被一个或多个取代基R 10取代; 并且R 2，R 3，R 4，R 5，R 7，R 6，R 8和R 10如权利要求中所定义。

公开(公告)号：US20100120798A1

公开(公告)日：2010-05-13

申请号：US12519993

申请日：2007-12-20

申请人： Steven John Woodhead ,  Christopher Hamlett ,  Marinus Leendert Verdonk ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Kwai Ming Cheung ,  John Caldwell ,  Tatiana Faria Da Fonseca McHardy ,  Richard William Arthur Luke ,  Zbigniew Stanley Matusiak ,  Gregory Richard Carr ,  Jeffrey James Morris

发明人： Steven John Woodhead ,  Christopher Hamlett ,  Marinus Leendert Verdonk ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Kwai Ming Cheung ,  John Caldwell ,  Tatiana Faria Da Fonseca McHardy ,  Richard William Arthur Luke ,  Zbigniew Stanley Matusiak ,  Gregory Richard Carr ,  Jeffrey James Morris

IPC分类号： A61K31/522 ,  A61K31/52 ,  C07D473/34 ,  A61P37/00 ,  A61P9/00 ,  A61P11/06 ,  A61P25/00 ,  A61P29/00 ,  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： 本发明提供具有式（I）的PKA和PKB激酶抑制化合物的式（I）化合物：GP 1 JT 2 JN 4 RNH（I）或其盐，溶剂合物，互变异构体或N-氧化物，其中（1） GP是组GP1：HET 2a a QG（HNCO）f 7（R）x N *（GP1）（2）GP是组GP2：10（R）r O 2a a QG（CH 2）w NVHN * ）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; 环V是5至10个环成员的单环或双环杂芳基; 并且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：US20100016340A1

公开(公告)日：2010-01-21

申请号：US12298338

申请日：2007-04-25

申请人： Steven John Woodhead ,  Christopher Hamlett ,  Hannah Fiona Sore ,  David Winter Walker ,  Marinus Leendert Verdonk ,  Ian Collins ,  John Caldwell ,  Kwai-Ming Cheung ,  Tatiana Faria Da Fonseca McHardy

发明人： Steven John Woodhead ,  Christopher Hamlett ,  Hannah Fiona Sore ,  David Winter Walker ,  Marinus Leendert Verdonk ,  Ian Collins ,  John Caldwell ,  Kwai-Ming Cheung ,  Tatiana Faria Da Fonseca McHardy

IPC分类号： A61K31/522 ,  C07D401/14 ,  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.

摘要翻译： 本发明提供式（I）化合物或其盐，溶剂化物，互变异构体或N-氧化物，其中J1-J2是CH-CH，N-CH，CH-N，HN-C（O）或CH 2 CO; T是N或CH，GP如权利要求中所定义。 该化合物具有作为PKA和PKB激酶抑制剂的活性，可用于治疗癌症。