公开(公告)号：US20090131470A1

公开(公告)日：2009-05-21

申请号：US11916485

申请日：2006-06-06

申请人： David Lee Walmsley ,  Martin James Drysdale ,  Christopher John Northfield ,  Christophe Fromont

发明人： David Lee Walmsley ,  Martin James Drysdale ,  Christopher John Northfield ,  Christophe Fromont

IPC分类号： A61K31/439 ,  C07D453/02 ,  A61K31/454 ,  C07D401/14 ,  A61P37/02

CPC分类号： C07D451/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D453/02 ,  C07D487/04

摘要： Compounds of formula (I) are inhibitors of PDK1 and CHK1 activity, and of use in the treatment of cancer and autoimmune disorders (I): wherein R2 is a radical of formula R7—(CH2)n−, or a radical of formula -Alk-N(—R5)—R9 wherein n is 0, 1, 2 or 3 and Alk is C1-C6 alkylene; R7 is (i) a heterocyclic ring of 5 or 6 ring atoms coupled via a ring carbon wherein the sole heteroatom is nitrogen, optionally substituted by C1-C6 alkyl or aryl C1-C6 alkyl, (ii) 1-aza-bicyclo[2.2.2]oct-3-yl, or (iii) 8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl; R8 and R9 are independently selected from hydrogen or C1-C3 alkyl; and the remaining substituents are as defined in the claims.

摘要翻译： 式（I）化合物是PDK1和CHK1活性的抑制剂，并且用于治疗癌症和自身免疫性疾病（I）：其中R2是式R7-（CH2）n-的基团，或式 - Alk-N（-R5）-R9，其中n为0,1,2或3，Alk为C1-C6亚烷基; R 7是（i）通过环碳连接的5或6个环原子的杂环，其中唯一杂原子是氮，任选被C 1 -C 6烷基或芳基C 1 -C 6烷基取代，（ii）1-氮杂 - 双环[2.2 .2]辛-3-基，或（iii）8-甲基-8-氮杂 - 双环[3.2.1]辛-3-基; R 8和R 9独立地选自氢或C 1 -C 3烷基; 而其余取代基如权利要求中所定义。

公开(公告)号：US20140094493A1

公开(公告)日：2014-04-03

申请号：US13983462

申请日：2012-02-06

申请人： Jillian G. Baker ,  Peter M. Fischer ,  Christophe Fromont ,  Sheila M. Gardiner ,  Stephen J. Hill ,  Gopal Jadhav ,  Barrie Kellam ,  Shailesh Mistry ,  Jeanette Woolard

发明人： Jillian G. Baker ,  Peter M. Fischer ,  Christophe Fromont ,  Sheila M. Gardiner ,  Stephen J. Hill ,  Gopal Jadhav ,  Barrie Kellam ,  Shailesh Mistry ,  Jeanette Woolard

IPC分类号： C07D405/14 ,  C07D319/20 ,  C07D211/38

CPC分类号： C07D405/14 ,  C07C217/34 ,  C07D209/46 ,  C07D211/38 ,  C07D215/20 ,  C07D217/24 ,  C07D241/40 ,  C07D309/06 ,  C07D319/20 ,  C07D405/12

摘要： A compound of Formula (I), and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein R1 is independently selected from F, Cl, Br, CN, NH2, OH, CHO, COOH, oxo, C1-4alkyl, C1-4alkoxy, CONH2 (optionally mono- or di-substituted by C1-4alkyl) and SO2NH2, R2 is independently selected from C1-6allkyl substituted by R3 wherein the C1-6alkyl chain optionally comprises one or two heteroatoms select from O; R3 is selected from aryl, C3-6cycloalkyl, C3-6heterocyclyl and C3-6heteroaryl, wherein the heterocyclyl and heteroaryl rings are nitrogen containing; and wherein R3 is optonally substituted by one or more groups selected from R1; n1 is zero or an integer from 1 to 2; n2 is an integer from 1 to 2; and the sum of n1 and 2 is less than or equal to 2; R5 is selected from any group defined for R1 and R2; R6a and R6b are independently selected from H or C1-4alkyl; R7 is independently selected from F, Cl, Br, CN, NH2, OH, CHO, COOH, oxo, C1-4alkyl, C1-4alkoxy, CONH2 (optionally mono- or di-substituted by C1-4alkyl) and SO2NH2, Q1, Q2 and Q3 are independently selected from H or any group defined for R1 and R2; or Q1 and Q2 or Q2 and Q3 together form a C5-6heteroaryl or C5-6heterocylclic ring; optionally containing one or two heteroatoms selected from N and O optionally substituted by any group selected from R5; Z is selected from linear C2-3 alkylene; X3 is O; X4 is selected from aryl, a 9-10 membered heteroaryl ring or a 9-10 membered heterocyclic ring, wherein the heteroaryl and heterocyclic rings contain one or more heteroatoms selected from N, and optionally additionally O, and wherein X4 is optionally substituted by one or two oxo moieties and is optionally substituted by one or more groups selected from R7; with the proviso that (i) when X4 is phenyl then Q1 and Q2 or Q2 and Q3—together form an optionally substituted heteroaryl or heterocylclic ring as defined above; and (ii) when Q1, Q2 and Q3 are independently selected from H or any group defined for R1 and R2 then X4 is not phenyl except when R2 is C1-5alkyl substituted by R3 wherein R3 is C3-6heterocyclyl as defined above, their preparation and novel intermediates, compositions thereof and their use in the prevention or treatment of cardiac and cardiovascular disease and methods for the treatment thereof.

公开(公告)号：US20130261178A1

公开(公告)日：2013-10-03

申请号：US13808493

申请日：2010-07-05

申请人： Shailesh Mistry ,  Etienne Daras ,  Christophe Fromont ,  Gopal Jadhav ,  Peter Martin Fischer ,  Barrie Kellam ,  Stephen John Hill ,  Jillian Glenda Baker

发明人： Shailesh Mistry ,  Etienne Daras ,  Christophe Fromont ,  Gopal Jadhav ,  Peter Martin Fischer ,  Barrie Kellam ,  Stephen John Hill ,  Jillian Glenda Baker

IPC分类号： C07C217/64 ,  C07C231/12 ,  C07C275/30 ,  C07C275/36 ,  C07C273/18 ,  C07D303/24 ,  C07C271/28 ,  C07C269/06 ,  C07C335/20 ,  C07C311/13 ,  C07C303/40 ,  C07C43/23 ,  C07C235/34 ,  C07C213/08

CPC分类号： C07C217/64 ,  C07C43/23 ,  C07C213/08 ,  C07C217/34 ,  C07C231/12 ,  C07C233/40 ,  C07C233/65 ,  C07C233/78 ,  C07C235/34 ,  C07C235/50 ,  C07C235/60 ,  C07C237/04 ,  C07C237/34 ,  C07C269/06 ,  C07C271/28 ,  C07C273/1854 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C275/36 ,  C07C275/40 ,  C07C275/42 ,  C07C303/40 ,  C07C311/13 ,  C07C335/16 ,  C07C335/20 ,  C07C2601/02 ,  C07C2601/08 ,  C07D303/24

摘要： A compound of formula I-0, and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein Z1 is C1-C4 linear or branched alkyl or alkenyl; R4 is selected from unsubstituted and substituted C3-C3 cycloalkyl, C1-C8 linear or branched alkyl, C2-5 alkenyl, C6-C10 heteroaryl or aryl, or C3-C8 heterocyclyl which may be part unsaturated, and combinations thereof; Z is linear C2-3 alkylene; X1 is selected from NH and O; X2 is selected from unsaturated C and unsaturated S; and X3 is selected from NH and CH2; or one of X1 and X3 is a single bond; or X1 is O and X2 and X3 together are a single bond; and R7 is selected from oxo, F, Cl, Br, CN, NH2, NR92, NO2, CF3, OR9, COR9, OCOR9, COOR9, NR9COR9, CONR92SO2NR92, NR9SO2R9; and R8 is selected from C1-5 alkyl, C1-5 alkoxyl, C2-5 alkenyl or alkynyl, C6-10 aryl and C3-8 cycloalkyl and combinations thereof, which may be unsubstituted or further substituted by one or more F, Cl, Br, CN, NH2, NR32, NO2, CF3; and R9 is selected from H and a group R8 as hereinbefore defined; n7 and n8 and the sum thereof are independently selected from zero and the whole number integer 1 to 4; processes for the preparation thereof, compositions and uses.

摘要翻译： 式I-0的化合物及其药学上可接受的盐或盐和生理上可水解的游离形式或盐形式的衍生物：其中Z1是C1-C4直链或支链烷基或烯基; R 4选自未取代和取代的C 3 -C 3环烷基，可以是部分不饱和的C 1 -C 8直链或支链烷基，C 2-5烯基，C 6 -C 10杂芳基或芳基或C 3 -C 8杂环基，及其组合; Z为直链C 2-3亚烷基; X1选自NH和O; X2选自不饱和C和不饱和S; 并且X 3选自NH和CH 2; 或者X1和X3中的一个是单键; 或X1为O，X2和X3一起为单键; 并且R 7选自氧代，F，Cl，Br，CN，NH 2，NR 92，NO 2，CF 3，OR 9，COR 9，OCOR 9，COOR 9，NR 9 COR 9，CONR 92 SO 2 NR 92，NR 9 SO 2 R 9; 并且R 8选自C 1-5烷基，C 1-5烷氧基，C 2-5烯基或炔基，C 6-10芳基和C 3-8环烷基及其组合，其可未取代或进一步被一个或多个F，Cl， Br，CN，NH 2，NR 32，NO 2，CF 3; 并且R 9选自H和上文定义的基团R 8; n7和n8，它们的和独立地选自零和整数1至4; 制备方法，组合物和用途。