公开(公告)号：WO2005121149A1

公开(公告)日：2005-12-22

申请号：PCT/GB2005/002318

申请日：2005-06-10

申请人： XENTION DISCOVERY LIMITED ,  FORD, John ,  PALMER, Nicholas, John ,  ATHERALL, John, Frederick ,  MADGE, David, John

发明人： FORD, John ,  PALMER, Nicholas, John ,  ATHERALL, John, Frederick ,  MADGE, David, John

IPC分类号： C07D491/04

CPC分类号： C07D491/04

摘要： A compound of formula (I) wherein R1 is aryl, heteroaryl, cycloalkyl or alkyl; R2 is H, alkyl, nitro, -CO 2 R7, CONR4R5 or halo; R3 is H, NR4R5, NC(O)R8, halo, trifluoromethyl, alkyl, nitrile or alkoxy; R4 and R5 may be the same or different, and may be H, alkyl, aryl, heteroaryl or cycloalkyl; or R4 and R5 may together form a saturated, unsaturated or partially saturated 4 to 7 member ring, wherein said ring may optionally comprise one or more further heteroatoms selected from N, O or S; X is O, S or NR6; R6 is H or alkyl; R7 is hydrogen, methyl or ethyl; R8 is methyl or ethyl; Ll is (CH 2 ) n , where n is 1,2 or 3; and Y is aryl, a heterocyclic group, alkyl, alkenyl or cycloalkyl; together with pharmaceutically acceptable salts thereof. The use of these compounds as potassium channel inhibitors is also described.

摘要翻译： 式（I）的化合物，其中R 1是芳基，杂芳基，环烷基或烷基; R2是H，烷基，硝基，-CO 2 R 7，CONR 4 R 5或卤素; R3是H，NR4R5，NC（O）R8，卤素，三氟甲基，烷基，腈或烷氧基; R 4和R 5可以相同或不同，并且可以是H，烷基，芳基，杂芳基或环烷基; 或R 4和R 5可以一起形成饱和的，不饱和的或部分饱和的4至7元环，其中所述环可任选地包含一个或多个选自N，O或S的其它杂原子; X是O，S或NR 6; R6是H或烷基; R7是氢，甲基或乙基; R8是甲基或乙基; L 1是（CH 2）n，其中n是1,2或3; Y为芳基，杂环基，烷基，链烯基或环烷基; 以及其药学上可接受的盐。 还描述了这些化合物作为钾通道抑制剂的用途。

公开(公告)号：WO2002083629A1

公开(公告)日：2002-10-24

申请号：PCT/GB2002/001733

申请日：2002-04-12

申请人： ARROW THERAPEUTICS LIMITED ,  CHANA, Surinder, Singh ,  COCKERILL, George, Stuart ,  MADGE, David

发明人： CHANA, Surinder, Singh ,  COCKERILL, George, Stuart ,  MADGE, David

IPC分类号： C07C311/08

CPC分类号： C07D333/54 ,  A01N41/06 ,  A01N43/18 ,  C07C311/21 ,  C07D333/34 ,  C07D333/38 ,  C07D409/12

摘要： Use of a bissulfonamide derivative of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in inhibiting the biosynthesis of aromatic amino acids via the shikimate pathway, wherein: R 1 and R 2 are the same or different and each represent hydrogen or alkyl or R 1 and R 2 together form a C 1 -c 3 alkylene group, -CO- or -CS-; R 3 and R 4 are the same or different and each represent -alkyl-aryl, -alkyl-heteroaryl, -alkenyl-aryl, -alkenyl-heteroalyl, -alkynyl-aryl-alkynylt-heteroaryl, aryl or heteroaryl; R 5 , R 7 and R 8 are the same or different and are hydrogen, halogen or hydroxy; and R 6 is furanyl, thienyl, imidazolyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, benzofuranyl or benzothienyl.

摘要翻译： 式（I）的双磺酰胺衍生物或其药学上可接受的盐在制备用于通过莽草酸通路抑制芳香族氨基酸的生物合成的药物中的用途，其中：R 1> 相同或不同，各自表示氢或烷基或R 1和R 2共同形成C 1 -C 3亚烷基，-CO-或-CS-; R 3和R 4相同或不同，并且各自表示 - 烷基 - 芳基， - 烷基 - 杂芳基 - - 烯基 - 芳基， - 烯基 - 杂芳基， - 炔基 - 芳基 - 炔基 - 杂芳基，芳基或杂芳基; R 5，R 7和R 8相同或不同，为氢，卤素或羟基; R 6是呋喃基，噻吩基，咪唑基，吡唑基，噻唑基，吡啶基，嘧啶基，苯并呋喃基或苯并噻吩基。

公开(公告)号：WO2010139967A8

公开(公告)日：2011-12-22

申请号：PCT/GB2010001123

申请日：2010-06-04

申请人： XENTION LTD ,  HAMLYN RICHARD JOHN ,  MADGE DAVID ,  MULLA MUSHTAQ ,  HARTZOULAKIS BASIL ,  JONES SIMON MARK ,  JOHN DEREK EDWARD

发明人： HAMLYN RICHARD JOHN ,  MADGE DAVID ,  MULLA MUSHTAQ ,  HARTZOULAKIS BASIL ,  JONES SIMON MARK ,  JOHN DEREK EDWARD

IPC分类号： C07D401/12 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/47 ,  A61P9/00 ,  A61P17/00 ,  C07D403/12

CPC分类号： C07D401/12 ,  C07D403/12

摘要： A compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein; A represents a chemical moiety with the general formula (II); X and Y are independently selected from a group consisting of CH2, CH(R5) or C(R5)(R6); R1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; R2 is selected from the group consisting of optionally substituted aryl or optionally substituted heteroaryl or NR7R8; R3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulfonyl or nitrile; R4 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl; R5 and R6 for each occurrence is optionally substituted alkyl; R7 and R8 are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; n = 0, 1, 2 or 3; o = 0, 1 or 2 with the proviso that when o = 0, n is 1, 2 or 3 and when o = 1, n is 1 or 2 is provided. Pharmaceutical compositions comprising the compounds are also provided. These compounds are useful in the treatment of various disorders including arrhythmia.

摘要翻译： 式（I）化合物或其盐或其药学上可接受的衍生物，其中： A表示具有通式（II）的化学部分; X和Y独立地选自由CH 2，CH（R 5）或C（R 5）（R 6）组成的组。 R 1选自任选取代的芳基烷基和任选取代的杂芳基烷基; R 2选自任选取代的芳基或任选取代的杂芳基或NR 7 R 8; R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基磺酰基或腈; R 4选自氢，任选取代的烷基，任选取代的环烷基，任选取代的杂环烷基，任选取代的酰基，任选取代的磺酰基，任选取代的氨磺酰基，任选取代的芳基，任选取代的芳烷基和任选取代的杂芳基; R5和R6每次出现是任选取代的烷基; R 7和R 8相同或不同，各自表示氢，任选取代的烷基，任选取代的环烷基，任选取代的芳烷基，任选取代的芳基或任选取代的杂芳基; n = 0,1,2或3; o = 0,1或2，条件是当o = 0时，n为1,2或3，当o = 1时，n为1或2。 还提供了包含该化合物的药物组合物。 这些化合物可用于治疗各种疾病，包括心律失常。

公开(公告)号：WO2010139953A1

公开(公告)日：2010-12-09

申请号：PCT/GB2010/001092

申请日：2010-06-04

申请人： XENTION LIMITED ,  HAMLYN, Richard, John ,  MADGE, David ,  MULLA, Mushtaq

发明人： HAMLYN, Richard, John ,  MADGE, David ,  MULLA, Mushtaq

IPC分类号： C07D209/46 ,  C07D217/24 ,  C07D401/12 ,  C07D403/12

CPC分类号： C07D209/46 ,  C07D217/24 ,  C07D401/12 ,  C07D403/12

摘要： A compound of formula (I): or its salts or pharmaceutically acceptable derivatives thereof wherein; A represents a chemical moiety with the general formula (II): X is selected from a group consisting of CH 2 , C(=O), CH(R 5 ), C(R 5 )(R 6 ) or C(R 5 )(R 6 )CH 2 ; R 1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; R 2 is selected from the group consisting of optionally substituted aryl or optionally substituted heteroaryl or NR 7 R 8 ; R 3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulfonyl or nitrile; R4 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl; R 5 and R 6 for each occurrence is optionally substituted alkyl; R 7 and R 8 are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; n = 1 or 2 is provided. Pharmaceutical compositions comprising the compounds are also provided. The compounds are useful in treating various conditions including arrhythmia.

摘要翻译： 式（I）的化合物或其盐或药学上可接受的衍生物，其中： A表示具有通式（II）的化学部分：X选自CH 2，C（= O），CH（R 5），C（R 5）（R 6）或C（R 5）（R 6）CH 2 ; R 1选自任选取代的芳基烷基和任选取代的杂芳基烷基; R 2选自任选取代的芳基或任选取代的杂芳基或NR 7 R 8; R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基磺酰基或腈; R 4选自氢，任选取代的烷基，任选取代的环烷基，任选取代的杂环烷基，任选取代的酰基，任选取代的磺酰基，任选取代的氨磺酰基，任选取代的芳基，任选取代的芳烷基和任选取代的杂芳基; R5和R6每次出现是任选取代的烷基; R 7和R 8相同或不同，各自表示氢，任选取代的烷基，任选取代的环烷基，任选取代的芳烷基，任选取代的芳基或任选取代的杂芳基; 提供n = 1或2。 还提供了包含该化合物的药物组合物。 该化合物可用于治疗各种病症，包括心律失常。

公开(公告)号：WO2010023448A1

公开(公告)日：2010-03-04

申请号：PCT/GB2009/002078

申请日：2009-08-27

申请人： XENTION LIMITED ,  JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  GARRETT, Sarah, Louise ,  HARTZOULAKIS, Basil ,  MADGE, David ,  FORD, John

发明人： JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  GARRETT, Sarah, Louise ,  HARTZOULAKIS, Basil ,  MADGE, David ,  FORD, John

IPC分类号： C07C311/21 ,  C07D205/04 ,  C07D211/08 ,  C07D213/04 ,  C07D231/00 ,  C07D233/54 ,  C07D265/28 ,  C07D271/12 ,  C07D277/32 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  A61K31/18 ,  A61P29/00

CPC分类号： C07C311/21 ,  C07C311/46 ,  C07C317/32 ,  C07C317/40 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D207/12 ,  C07D209/08 ,  C07D211/16 ,  C07D211/34 ,  C07D211/44 ,  C07D213/36 ,  C07D213/40 ,  C07D213/71 ,  C07D231/12 ,  C07D231/18 ,  C07D231/56 ,  C07D233/61 ,  C07D233/64 ,  C07D233/84 ,  C07D265/30 ,  C07D265/36 ,  C07D271/08 ,  C07D277/28 ,  C07D277/36 ,  C07D277/46 ,  C07D285/12 ,  C07D285/135 ,  C07D307/79 ,  C07D311/70 ,  C07D317/62 ,  C07D319/18 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12

摘要： The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein; X 1 is selected from a group consisting of CH 2 , C(=O), C(=NH), NC(=O), R 1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl R 2 is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl or heteroaryl or NR 24 R 25 , R 3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulfonyl or nitrile; R 4 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl R 5 may be hydrogen, an optionally substituted alkyl, preferably CH 3 or, NR 4 R 5 may form an optionally substituted saturated or partially saturated 4-7 membered ring with the general formula (II). Wherein; X 2 is C(=O), CH 2 , CH(R 6 ) or C(R 6 )(R 6 ), X 3 is CH 2 , CH(R 7 ), C(R 7 )(R 7 ), NH, N(R 8 ), O or S Each R 6 independently represents optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; Each R 7 independently represents optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl R 8 is optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R 24 and R 25 are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl, n = 1 or 2 m = 1, 2 or 3 With the proviso that when X 1 is C=O and R 5 is H then R 4 is not (a) or (b) or (c). Where R 4 a, R 5 a and R 6 a are each independently H, C 1-6 alkyl, aryl, heteroaryl, cycloalkyl, or aryl-C 1-6 alkyl; R 10 a is H or C 1-6 alkyl; and R 11 a is C 1-6 alkyl or aryl-C 1-6 alkyl and when X 1 is C=O or CH 2 and R 5 is H then R 4 is not (d) Where q is 0 to 5, R 3 b is H, OH or alkoxy and R 4 b is NH 2 , phenyl or a C 3-10 heterocycle. The compounds are useful as potassium ion channel inhibitors.

摘要翻译： 本发明提供式（I）化合物或其盐或其药学上可接受的衍生物，其中： X 1选自CH 2，C（= O），C（= NH），NC（= O），R 1选自任选取代的芳烷基和任选取代的杂芳基烷基R 2选自基团 由任选取代的烷基，任选取代的芳基或杂芳基或NR 24 R 25组成，R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基磺酰基或腈; R 4选自任选取代的烷基，任选取代的环烷基，任选取代的杂环烷基，任选取代的酰基，任选取代的磺酰基，任选取代的氨磺酰基，任选取代的芳基，任选取代的芳基烷基和任选取代的杂芳基R 5可以是氢， 任选取代的烷基，优选CH 3或NR 4 R 5可以形成具有通式（II）的任选取代的饱和或部分饱和的4-7元环。 其中： X2是C（= O），CH2，CH（R6）或C（R6）（R6），X3是CH2，CH（R7），C（R7）（R7），NH，N（R8） 每个R 6独立地表示任选取代的氨基，任选取代的氨基羰基，羟基，任选取代的酰基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; 每个R 7独立地表示任选取代的氨基，任选取代的氨基羰基，羟基，任选取代的酰基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基R 8是任选取代的 酰基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; R 24和R 25相同或不同，各自表示氢，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基，n = 1或2 m = 1,2或3，条件是当 X1为C = O，R5为H，R4不为（a）或（b）或（c）。 其中R 4a，R 5a和R 6a各自独立地为H，C 1-6烷基，芳基，杂芳基，环烷基或芳基-C 1-6烷基; R10a是H或C1-6烷基; R 11a为C 1-6烷基或芳基-C 1-6烷基，当X 1为C = O或CH 2且R 5为H时，R 4不为（d）其中q为0至5，R 3b为H，OH或烷氧基，R 4b为NH 2 ，苯基或C 3-10杂环。 该化合物可用作钾离子通道抑制剂。

公开(公告)号：WO0128537A3

公开(公告)日：2001-06-14

申请号：PCT/GB0003944

申请日：2000-10-13

申请人： ARROW THERAPEUTICS LTD ,  MADGE DAVID ,  WISHART GRANT ,  DOLMAN MARK ,  MAUNDER PETER

发明人： MADGE DAVID ,  WISHART GRANT ,  DOLMAN MARK ,  MAUNDER PETER

IPC分类号： C07D239/74 ,  A01N41/06 ,  A61K31/145 ,  A61K31/18 ,  A61K31/381 ,  A61K31/422 ,  A61K31/425 ,  A61K31/426 ,  A61K31/4436 ,  A61K31/517 ,  A61L2/18 ,  A61P31/04 ,  A61P31/10 ,  A61P33/06 ,  A61P43/00 ,  C07C311/13 ,  C07C311/21 ,  C07C311/29 ,  C07C311/46 ,  C07C317/14 ,  C07D333/34 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

CPC分类号： A61K31/18 ,  C07C311/13 ,  C07C311/21 ,  C07C311/29 ,  C07C311/46 ,  C07C317/14

摘要： Bissulfonamide derivatives of formula (I) are capable of inhibiting: a) the biosynthesis of aromatic amino acids via the shikimate pathway and b) the catabolism of quinic acid, wherein: Ar is an aryl or heteroaryl group; R1 and R2 are the same or different and each represent hydrogen or alkyl or R1 and R2 together form a C1-C3 alkylene group, -CO- or -CS-; and R3 and R4 are the same or different and each represent -alkyl-aryl, -alkyl-heteroaryl, -alkenyl-aryl, -alkenyl-heteroaryl, -alkynyl-aryl-alkynyl-heterorayl, aryl or heteroaryl.

摘要翻译： 式（I）的双磺酰胺衍生物能够抑制：a）通过莽草酸通路生物合成芳族氨基酸，和b）奎尼酸的分解代谢，其中：Ar是芳基或杂芳基; R 1和R 2相同或不同，各自表示氢或烷基，或者R 1和R 2一起形成C 1 -C 3亚烷基-CO-或-CS-; 并且R 3和R 4相同或不同，并且各自表示 - 烷基 - 芳基， - 烷基 - 杂芳基 - - 烯基 - 芳基， - 烯基 - 杂芳基 - - 炔基 - 芳基 - 炔基 - 杂芳基，芳基或杂芳基。

公开(公告)号：WO2010139967A1

公开(公告)日：2010-12-09

申请号：PCT/GB2010/001123

申请日：2010-06-04

申请人： XENTION LIMITED ,  HAMLYN, Richard, John ,  MADGE, David ,  MULLA, Mushtaq

发明人： MADGE, David ,  MULLA, Mushtaq

IPC分类号： C07D401/12 ,  C07D403/12 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/47 ,  A61P9/00 ,  A61P17/00

CPC分类号： C07D401/12 ,  C07D403/12

摘要： A compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein; A represents a chemical moiety with the general formula (II); X and Y are independently selected from a group consisting of CH 2 , CH(R 5 ) or C(R 5 )(R 6 ); R 1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; R 2 is selected from the group consisting of optionally substituted aryl or optionally substituted heteroaryl or NR 7 R 8 ; R 3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulfonyl or nitrile; R 4 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl; R 5 and R 6 for each occurrence is optionally substituted alkyl; R 7 and R 8 are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; n = 0, 1, 2 or 3; o = 0, 1 or 2 with the proviso that when o = 0, n is 1, 2 or 3 and when o = 1, n is 1 or 2 is provided. Pharmaceutical compositions comprising the compounds are also provided. These compounds are useful in the treatment of various disorders including arrhythmia.

摘要翻译： 式（I）化合物或其盐或其药学上可接受的衍生物，其中： A表示具有通式（II）的化学部分; X和Y独立地选自由CH 2，CH（R 5）或C（R 5）（R 6）组成的组。 R 1选自任选取代的芳烷基和任选取代的杂芳基烷基; R 2选自任选取代的芳基或任选取代的杂芳基或NR 7 R 8; R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基磺酰基或腈; R 4选自氢，任选取代的烷基，任选取代的环烷基，任选取代的杂环烷基，任选取代的酰基，任选取代的磺酰基，任选取代的氨磺酰基，任选取代的芳基，任选取代的芳基烷基和任选取代的杂芳基; R5和R6各为任意取代的烷基; R7和R8相同或不同，各自表示氢，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; n = 0,1,2或3; o = 0,1或2，条件是当o = 0时，n为1,2或3，当o = 1时，n为1或2。 还提供了包含该化合物的药物组合物。 这些化合物可用于治疗各种疾病，包括心律失常。

公开(公告)号：WO2010023446A1

公开(公告)日：2010-03-04

申请号：PCT/GB2009/002076

申请日：2009-08-27

申请人： XENTION LIMITED ,  JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  JONES, Simon, Mark ,  HARTZOULAKIS, Basil ,  MADGE, David ,  FORD, John

发明人： JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  JONES, Simon, Mark ,  HARTZOULAKIS, Basil ,  MADGE, David ,  FORD, John

IPC分类号： C07C311/21 ,  C07D213/71 ,  C07D231/18 ,  C07D233/84 ,  C07D233/90 ,  C07D403/12 ,  C07D413/12 ,  C07D295/135 ,  C07D207/27 ,  A61K31/18 ,  A61P29/00

CPC分类号： C07C311/21 ,  C07D207/27 ,  C07D213/71 ,  C07D231/18 ,  C07D233/84 ,  C07D233/90 ,  C07D295/135 ,  C07D403/12 ,  C07D413/12

摘要： The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives thereof wherein; X 1 is selected from a group consisting of CH, O or N; R 1 is selected from the group consisting of optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; R 2 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl or NR 6 R 7 ; R 3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino sulphonyl or nitrile; R 4 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted acyl, optionally substituted sulfonyl, optionally substituted sulfamoyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroaryl R 5 may be hydrogen or may, together with R 4 and X 1 (when X 1 = N), form an optionally substituted saturated or partially saturated 5-7 membered ring with the general formula (II). X 2 is C(=O), C(R 8 ) 2 ; X 3 is, C(R 9 ) 2 , N(R 9b ), O or S; R 6 and R 7 are the same or different and each represents hydrogen, optioanally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R 8a and R 8b for each occurence is independently hydrogen, halogen, optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; R 9a R 9b for each occurence is independently hydrogen, halogen, optionally substituted amino, optionally substituted amino carbonyl, hydroxyl, optionally substituted acyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; R 9c is optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; With the proviso that: When X 1 is O then j = 0 When X 1 is N or CH then j =1 n = 1,2 or 3. The compounds are useful as potassium ion channel inhibitors.

摘要翻译： 本发明提供式（I）化合物或其盐或其药学上可接受的衍生物，其中： X1选自CH，O或N; R 1选自任选取代的芳基烷基和任选取代的杂芳基烷基; R 2选自任选取代的芳基，任选取代的杂芳基或NR 6 R 7; R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基磺酰基或腈; R 4选自任选取代的烷基，任选取代的环烷基，任选取代的杂环烷基，任选取代的酰基，任选取代的磺酰基，任选取代的氨磺酰基，任选取代的芳基，任选取代的芳烷基和任选取代的杂芳基R 5可以是氢或可以 与R4和X1一起（当X1 = N时）与通式（II）形成任选取代的饱和或部分饱和的5-7元环。 X2为C（= O），C（R8）2; X3为，C（R9）2，N（R9b），O或S; R6和R7相同或不同，各自代表氢，视黄醛取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; R8a和R8b各自独立地为氢，卤素，任选取代的氨基，任选取代的氨基羰基，羟基，任选取代的酰基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或 任选取代的杂芳基; R9a R9b各自独立地为氢，卤素，任选取代的氨基，任选取代的氨基羰基，羟基，任选取代的酰基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或 任选取代的杂芳基; 任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; 条件是：当X1为O时，j = 0当X1为N或CH时，则j = 1 n = 1,2或3.该化合物可用作钾离子通道抑制剂。

公开(公告)号：WO2004111057A1

公开(公告)日：2004-12-23

申请号：PCT/GB2004/002454

申请日：2004-06-10

申请人： XENTION DISCOVERY LIMITED ,  FORD, John ,  PALMER, Nicholas, John ,  ATHERALL, John, Frederick ,  MADGE, David, John ,  SHERBORNE, Brad ,  BUSHFIELD, Mark ,  STEVENS, Edward, Benedict

发明人： FORD, John ,  PALMER, Nicholas, John ,  ATHERALL, John, Frederick ,  MADGE, David, John ,  SHERBORNE, Brad ,  BUSHFIELD, Mark ,  STEVENS, Edward, Benedict

IPC分类号： C07D495/04

CPC分类号： C07D495/04 ,  A61K31/495

摘要： The present invention provides thienopyrimidine compounds which are potasium channels inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also provided.

摘要翻译： 本发明提供作为钾通道抑制剂的噻吩并嘧啶化合物。 还提供了包含该化合物的药物组合物及其在治疗心律失常中的用途。

公开(公告)号：WO2010023445A1

公开(公告)日：2010-03-04

申请号：PCT/GB2009/002075

申请日：2009-08-27

申请人： XENTION LIMITED ,  JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  JONES, Simon, Mark ,  POLLARD, Derek, Roland ,  HARTZOULAKIS, Basil ,  PAYNE, Helen ,  MADGE, David ,  FORD, John

发明人： JOHN, Derek, Edward ,  MULLA, Mushtaq ,  HAMLYN, Richard, John ,  JONES, Simon, Mark ,  POLLARD, Derek, Roland ,  HARTZOULAKIS, Basil ,  PAYNE, Helen ,  MADGE, David ,  FORD, John

IPC分类号： C07D211/08 ,  C07D217/16 ,  C07D231/18 ,  C07D233/84 ,  C07D265/30 ,  C07D277/36 ,  C07D307/64 ,  C07D311/58 ,  C07D333/34 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D295/192 ,  A61K31/18 ,  A61P29/00

CPC分类号： C07D295/18 ,  C07D207/12 ,  C07D211/10 ,  C07D211/16 ,  C07D211/22 ,  C07D211/48 ,  C07D211/52 ,  C07D217/20 ,  C07D231/18 ,  C07D233/84 ,  C07D241/04 ,  C07D265/30 ,  C07D277/36 ,  C07D307/64 ,  C07D311/58 ,  C07D333/34

摘要： The present invention provides a compound of formula (I):or its salts or pharmaceutically acceptable derivatives wherein; R 1 is selected from the group consisting of optionally substituted arylalkyl, optionally substituted aryl, optionally substituted heteroarylalkyl and optionally substituted heteroaryl; R 2 is selected from the group consisting of optionally substituted acyl, optionally substituted sulfonyl and optionally substituted sulfamoyl; R 3 is selected from the group consisting of hydrogen, halogen, hydroxyl, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino carbonyl, optionally substituted amino sulfonyl or nitrile; X 1 is selected from a group consisting of a chemical bond, CR 7 R 8 , C(=O), C(=NH), NR 9 , NHC(O), and SO 2 wherein; R 7 and R 8 are independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl or; R 7 and R 8 together form an optionally substituted C 4-6 cycloalkyl ring; R 9 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aryl and optionally substituted heteroaryl; A represents an optionally substituted saturated or partially saturated 4-7 membered ring with the general formula (A): or is selected from formula (B): For each occurrence; X 2 is CH or N; X 3 is CH 2 , CH(R 5a ), C(R 5a )(R 5b ), NH, N(R 5c ), O or S; X 4 is independently selected from C(=O), CH 2 , CH(R 4a ) or C(R 4a )(R 4b ); R 4a and R 4b for each occurrence is independently halogen, optionally substituted amino, hydroxyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R 5a and R 5b for each occurrence is independently, halogen, optionally substituted amino, hydroxyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted alkanoyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; R 5c is optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; n = 1 or 2. The compounds are useful as potassium ion channel inhibitors.

摘要翻译： 本发明提供式（I）化合物或其盐或药学上可接受的衍生物，其中： R 1选自任选取代的芳基烷基，任选取代的芳基，任选取代的杂芳基烷基和任选取代的杂芳基; R 2选自任选取代的酰基，任选取代的磺酰基和任选取代的氨磺酰基; R 3选自氢，卤素，羟基，烷氧基，芳氧基，任选取代的烷基，任选取代的氨基，任选取代的氨基羰基，任选取代的氨基磺酰基或腈; X 1选自由化学键，CR 7 R 8，C（= O），C（= NH），NR 9，NHC（O）和SO 2组成的组。 R 7和R 8独立地选自氢，任选取代的烷基，任选取代的环烷基，任选取代的芳基和任选取代的杂芳基;或 R7和R8一起形成任选取代的C 4-6环烷基环; R9选自氢，任选取代的烷基，任选取代的芳基和任选取代的杂芳基; A表示任选取代的具有通式（A）的饱和或部分饱和的4-7元环：或选自式（B）：每次出现; X2是CH或N; X3是CH2，CH（R5a），C（R5a）（R5b），NH，N（R5c），O或S; X4独立地选自C（= O），CH2，CH（R4a）或C（R4a）（R4b）; R4a和R4b各自独立地为卤素，任选取代的氨基，羟基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; R5a和R5b各自独立地为卤素，任选取代的氨基，羟基，任选取代的烷氧基，任选取代的芳氧基，任选取代的烷基，任选取代的烷酰基，任选取代的环烷基，任选取代的芳基烷基，任选取代的芳基或任选取代的杂芳基; 任选取代的烷基，任选取代的环烷基，任选取代的芳烷基，任选取代的芳基或任选取代的杂芳基; n = 1或2.化合物可用作钾离子通道抑制剂。