公开(公告)号：EP1651612B9

公开(公告)日：2012-09-05

申请号：EP04743512.8

申请日：2004-07-22

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio 436 Cambridge Science Park ,  O'BRIEN, Michael, Alistair ,  CARR, Maria, Grazia 436 Cambridge Science Park ,  EARLY, Theresa, Rachel 436 Cambridge Science Park ,  GILL, Adrian.L. 436 Cambridge Science Park ,  TREWARTHA, Gary 436 Cambridge Science Park ,  WOOLFORD, Alison, Jo-Anne ,  WOODHEAD, Andrew, James ,  WYATT, Paul, Graham 436 Cambridge Science Park

IPC分类号： C07D231/38 ,  C07D231/42 ,  C07D403/12 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D401/14 ,  A61K31/4155 ,  A61P35/00 ,  A61P31/10 ,  A61P31/12 ,  A61P37/00 ,  A61P25/28

CPC分类号： C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

公开(公告)号：EP1651612B1

公开(公告)日：2012-04-11

申请号：EP04743512.8

申请日：2004-07-22

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio 436 Cambridge Science Park ,  O'BRIEN, Michael, Alistair ,  CARR, Maria, Grazia 436 Cambridge Science Park ,  EARLY, Theresa, Rachel 436 Cambridge Science Park ,  GILL, Adrian.L. 436 Cambridge Science Park ,  TREWARTHA, Gary 436 Cambridge Science Park ,  WOOLFORD, Alison, Jo-Anne ,  WOODHEAD, Andrew, James ,  WYATT, Paul, Graham 436 Cambridge Science Park

IPC分类号： C07D231/38 ,  C07D231/42 ,  C07D403/12 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D401/14 ,  A61K31/4155 ,  A61P35/00 ,  A61P31/10 ,  A61P31/12 ,  A61P37/00 ,  A61P25/28

CPC分类号： C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

摘要： The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. Formula (0). In formula (0): X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

公开(公告)号：EP1648426B1

公开(公告)日：2014-01-08

申请号：EP04743172.1

申请日：2004-07-05

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio 436 Cambridge Science Park ,  O'BRIEN, Michael, Alistair ,  CARR, Maria, Grazia ,  EARLY, Theresa, Rachel ,  NAVARRO, Eva, Figueroa ,  GILL, Adrian, Liam ,  HOWARD, Steven ,  TREWARTHA, Gary ,  WOOLFORD, Alison, Jo-Anne ,  WOODHEAD, Andrew, James ,  WYATT, Paul

IPC分类号： A61K31/4184 ,  C07D403/04 ,  A61P35/00 ,  A61P31/10

CPC分类号： A61K31/5377 ,  A61K31/00 ,  A61K31/4184 ,  A61K45/06 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D513/04

公开(公告)号：EP1877379B1

公开(公告)日：2013-01-16

申请号：EP06726780.7

申请日：2006-04-13

申请人： Astex Therapeutics Limited

发明人： CHESSARI, Gianni ,  CONGREVE, Miles, Stuart ,  NAVARRO, Eva, Figueroa ,  FREDERICKSON, Martyn ,  MURRAY, Christopher ,  WOOLFORD, Alison, Jo-Anne ,  CARR, Maria, Grazia ,  DOWNHAM, Robert ,  O'BRIEN, Michael, Alistair ,  PHILLIPS, Theresa, Rachel ,  WOODHEAD, Andrew, James

IPC分类号： C07D209/44 ,  C07D209/08 ,  C07D215/08 ,  C07D491/10 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D401/04 ,  C07D401/12 ,  A61K31/438 ,  A61K31/439 ,  A61K31/403

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

公开(公告)号：EP1648449A2

公开(公告)日：2006-04-26

申请号：EP04743256.2

申请日：2004-07-05

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio ,  WOODHEAD, Andrew, James ,  WYATT, Paul, Graham ,  O'BRIEN, Michael, Alistair ,  NAVARRO, Eva, Figueroa

IPC分类号： A61K31/4184 ,  C07D403/04 ,  A61P35/00 ,  A61P31/10

CPC分类号： C07D401/14 ,  A61K31/00 ,  A61K31/4184 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

摘要： The invention provides a compound of the formula (I) or a salt, N-oxide or solvate thereof. The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases.

公开(公告)号：EP2773613A1

公开(公告)日：2014-09-10

申请号：EP12791446.3

申请日：2012-10-31

申请人： Astex Therapeutics Limited

发明人： WOODHEAD, Andrew, James ,  CHESSARI, Gianni ,  BESONG, Gilbert, Ebai ,  CARR, Maria, Grazia ,  HISCOCK, Steven, Douglas ,  O'BRIEN, Michael, Alistair ,  REES, David, Charles ,  SAALAU-BETHELL, Susanne, Maria ,  WILLEMS, Hendrika, Maria, Gerarda ,  THOMPSON, Neil, Thomas

IPC分类号： C07D209/14 ,  C07D213/75 ,  C07D231/12 ,  C07D233/24 ,  C07D233/64 ,  C07D295/02 ,  C07D305/06 ,  C07D305/08 ,  C07D309/14 ,  C07C217/58 ,  A61P31/12 ,  A61K31/137 ,  A61K31/44 ,  A61K31/415 ,  A61K31/4164

CPC分类号： A61K31/505 ,  A61K31/135 ,  A61K31/137 ,  A61K31/165 ,  A61K31/397 ,  A61K31/4409 ,  A61K31/4462 ,  A61K31/4465 ,  A61K45/06 ,  C07B2200/05 ,  C07C217/58 ,  C07C217/60 ,  C07C217/62 ,  C07C217/74 ,  C07C217/90 ,  C07C225/12 ,  C07C233/18 ,  C07C233/25 ,  C07C235/46 ,  C07C237/04 ,  C07C237/06 ,  C07C237/08 ,  C07C237/10 ,  C07C237/12 ,  C07C237/20 ,  C07C243/34 ,  C07C251/48 ,  C07C255/24 ,  C07C255/29 ,  C07C255/37 ,  C07C255/46 ,  C07C255/54 ,  C07C259/06 ,  C07C271/12 ,  C07C275/36 ,  C07C311/04 ,  C07C311/08 ,  C07C311/29 ,  C07C313/06 ,  C07C317/22 ,  C07C323/25 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/16 ,  C07D205/04 ,  C07D207/14 ,  C07D207/335 ,  C07D209/08 ,  C07D209/14 ,  C07D209/44 ,  C07D211/26 ,  C07D211/56 ,  C07D211/70 ,  C07D213/38 ,  C07D213/64 ,  C07D213/65 ,  C07D213/68 ,  C07D213/73 ,  C07D213/74 ,  C07D213/75 ,  C07D213/81 ,  C07D213/84 ,  C07D217/02 ,  C07D231/12 ,  C07D233/24 ,  C07D233/64 ,  C07D237/14 ,  C07D239/34 ,  C07D239/42 ,  C07D241/18 ,  C07D241/20 ,  C07D241/24 ,  C07D243/14 ,  C07D263/32 ,  C07D265/36 ,  C07D271/10 ,  C07D277/68 ,  C07D285/13 ,  C07D295/02 ,  C07D295/027 ,  C07D295/185 ,  C07D295/192 ,  C07D305/06 ,  C07D305/08 ,  C07D307/14 ,  C07D307/22 ,  C07D307/79 ,  C07D309/06 ,  C07D309/12 ,  C07D309/14 ,  C07D319/18 ,  C07D513/04

摘要： The invention provides compounds of the formula (I): or a salt, N-oxide or tautomer thereof, wherein A is CH, CF or nitrogen; E is CH, CF or nitrogen; and R
0 is hydrogen or C
1-2 alkyl; R
1a is selected from CONH
2 ; CO
2 H; an optionally substituted acyclic C
1-8 hydrocarbon group; and an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S; R
2 is selected from hydrogen and a group R
2a ; R
2a is selected from an optionally substituted acyclic d-8 hydrocarbon group; an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1 or 2 ring members are heteroatom ring members selected from O, N and S; and an optionally substituted bicyclic heterocyclic group of 9 or 10 ring members, of which 1 or 2 ring members are nitrogen atoms; wherein at least one of R
1 and R
2 is other than hydrogen; R
3 is an optionally substituted 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0, 1, 2 or 3 heteroatom ring members selected from N, O and S; R
4a is selected from halogen; cyano; C
1-4 alkyl optionally substituted with one or more fluorine atoms; C
1-4 alkoxy optionally substituted with one or more fluorine atoms; hydroxy-C
1-4 alkyl; and C
1-2 alkoxy-C
1-4 alkyl; R
5 is selected from hydrogen and a substituent R
5a ; and R
5a is selected from C
1-2 alkyl optionally substituted with one or more fluorine atoms; C
1-3 alkoxy optionally substituted with one or more fluorine atoms; halogen; cyclopropyl; cyano; and amino, The compounds have activity against hepatitis C virus and can be used in the prevention or treatment of hepatitis C viral infections.

摘要翻译： 本发明提供了式（6）的化合物：或其盐，N-氧化物或互变异构体，worin甲氮是CH，CF或; E是CH，CF或氮; 和R0是氢或C1-2烷基; R 1a为从CONH2选择; CO 2 H; 任选substituiertem C1-8无环烃基; 在任选取代的碳或3至7个环成员，其中为0，1，2，3或4个是选自O，N和S的杂原子环成员的杂环单环基团; R 2选自氢和基团R 2a中选择; R 2a为从在OPTIONALLY substituiertem非环状C 1-8烃基; 任选的单环取代的碳环或3至7个环成员，其中为0，1或2个环成员是选自O，N和S的杂原子环成员的杂环基团; 并以9个或10个环成员任选取代的双环杂环基团，其中1名或2个环成员是氮原子; worin的R1和R2是氢以外的至少一个; R 3是任选取代的3元至10元单环或双环杂环或碳环含有0,1，1,2或3个选自N，O和S的杂原子环成员; R 4a为选自卤素; 氰基; C 1-4烷基任选被一个或多个氟原子substituiertem; C 1-4烷氧基任选被一个或多个氟原子substituiertem; 羟基C 1-4烷基; 和C 1-2烷氧基-C 1-4烷基; R5选自氢和取代基中，R 5a选择; 和R 5a从C1-2烷基，其任选substituiertem选择具有一个或多个氟原子; C 1-3烷氧基任选被一个或多个氟原子substituiertem; 卤素; 环丙基; 氰基; 和氨基酸。 所述化合物具有抗丙型肝炎病毒活性，并且可以在用于预防或治疗丙型肝炎病毒感染的使用。

公开(公告)号：EP2114941A1

公开(公告)日：2009-11-11

申请号：EP07848659.4

申请日：2007-12-21

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio ,  BESONG, Gilbert, Ebai ,  CALLAGHAN, Owen ,  CARR, Maria, Grazia ,  CONGREVE, Miles, Stuart ,  GILL, Adrian, Liam ,  GRIFFITHS-JONES, Charlotte, Mary ,  MADIN, Andrew ,  MURRAY, Christopher, William ,  NIJJAR, Rajdeep, Kaur ,  O'BRIEN, Michael, Alistair ,  PIKE, Andrew ,  SAXTY, Gordon ,  TAYLOR, Richard, David ,  VICKERSTAFFE, Emma

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

CPC分类号： C07D487/04 ,  A61K31/437 ,  C07D471/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

公开(公告)号：EP1877379A1

公开(公告)日：2008-01-16

申请号：EP06726780.7

申请日：2006-04-13

申请人： Astex Therapeutics Limited

发明人： CHESSARI, Gianni ,  CONGREVE, Miles, Stuart ,  NAVARRO, Eva, Figueroa ,  FREDERICKSON, Martyn ,  MURRAY, Christopher ,  WOOLFORD, Alison, Jo-Anne ,  CARR, Maria, Grazia ,  DOWNHAM, Robert ,  O'BRIEN, Michael, Alistair ,  PHILLIPS, Theresa, Rachel ,  WOODHEAD, Andrew, James

IPC分类号： C07D209/44 ,  C07D209/08 ,  C07D215/08 ,  C07D491/10 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D401/04 ,  C07D401/12 ,  A61K31/438 ,  A61K31/439 ,  A61K31/403

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

摘要： The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl- amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The compounds have activity as Hsp90 inhibitors.

摘要翻译： 本发明提供了式（I）的化合物：或其盐，互变异构体，溶剂合物和N-氧化物; 其中R1是羟基或氢; R2是羟基; 甲氧基或氢; 条件是R1和R2中的至少一个是羟基; R3选自氢; 卤素; 氰基; 任选取代的C 1-5烃基和任选取代的C 1-5烃氧基; R4选自氢; 基团 - （O）n -R 7，其中n是0或1并且R 7是任选取代的无环C 1-5烃基或具有3至7个环成员的单环碳环或杂环基团; 卤素; 氰基; 羟基; 氨基; 和任选取代的单 - 或二-C1-5烃基 - 氨基; 或R3和R4一起形成5至7个环成员的单环碳环或杂环; 并且NR 5 R 6形成任选取代的具有8至12个环成员的双环杂环基团，其中至多5个环成员为选自氧，氮和硫的杂原子。 这些化合物具有Hsp90抑制剂的活性。

公开(公告)号：EP1836188A1

公开(公告)日：2007-09-26

申请号：EP05823522.7

申请日：2005-12-30

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio ,  O'BRIEN, Michael, Alistair ,  CARR, Maria, Grazia ,  DAVIES, Nicholas, Gareth, Morse ,  GILL, Adrian, Liam ,  NAVARRO, Eva, Figueroa ,  HOWARD, Steven ,  TREWARTHA, Gary ,  WOODHEAD, Andrew, James ,  WOOLFORD, Alison, Jo-Anne ,  WYATT, Paul, Graham

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D417/04 ,  C07D413/04 ,  C07D471/04 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/427 ,  A61P35/00

CPC分类号： C07D407/14 ,  C07D231/40 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/04 ,  C07D417/04 ,  C07D471/04

摘要： The invention provides a compound of the formula (I): for use in medicine: or salts or tautomers or N-oxides or solvates thereof; wherein R1 is an optionally substituted heterocyclic group having from 3 to 12 ring members provided that the cyclic group joined to the pyrazole contains at least one heteroatom selected from N, O or S; A is a bond or -Y-(B)n-; B is C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; n is 0 or 1; Y is a bond or an alkylene chain of 1,2 or 3 carbon atoms in length; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from optionally substituted carbocyclic and heterocyclic groups having from 3 to 12 ring members or an optionally substituted C1-8 hydrocarbyl group; with the proviso that R1 is not formula (II): where X, R3’ and R4’ are defined in the claims.

公开(公告)号：EP2114941B1

公开(公告)日：2015-03-25

申请号：EP07848659.4

申请日：2007-12-21

申请人： Astex Therapeutics Limited

发明人： BERDINI, Valerio ,  BESONG, Gilbert, Ebai ,  CALLAGHAN, Owen ,  CARR, Maria, Grazia ,  CONGREVE, Miles, Stuart ,  GILL, Adrian, Liam ,  GRIFFITHS-JONES, Charlotte, Mary ,  MADIN, Andrew ,  MURRAY, Christopher, William ,  NIJJAR, Rajdeep, Kaur ,  O'BRIEN, Michael, Alistair ,  PIKE, Andrew ,  SAXTY, Gordon ,  TAYLOR, Richard, David ,  VICKERSTAFFE, Emma

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

CPC分类号： C07D487/04 ,  A61K31/437 ,  C07D471/04