公开(公告)号：WO2012104659A1

公开(公告)日：2012-08-09

申请号：PCT/GB2012/050246

申请日：2012-02-06

Applicant: UNIVERSITY OF NOTTINGHAM ,  BAKER, Jillian G. ,  FISCHER, Peter M. ,  FROMONT, Christophe ,  GARDINER, Sheila M. ,  HILL, Stephen J. ,  JADHAV, Gopal ,  KELLAM, Barrie ,  MISTRY, Shailesh ,  WOOLARD, Jeanette

Inventor： BAKER, Jillian G. ,  FISCHER, Peter M. ,  FROMONT, Christophe ,  GARDINER, Sheila M. ,  HILL, Stephen J. ,  JADHAV, Gopal ,  KELLAM, Barrie ,  MISTRY, Shailesh ,  WOOLARD, Jeanette

IPC: C07D209/46 ,  C07D211/38 ,  C07D215/20 ,  C07D217/24 ,  C07D241/40 ,  C07D309/06 ,  C07D319/20 ,  C07D405/12 ,  C07D405/14 ,  C07C217/54 ,  A61K31/498 ,  A61K31/4725 ,  A61K31/357 ,  A61K31/445 ,  A61K31/4035

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

Abstract: A compound of Formula (I), and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein R 1 is independently selected from F, CI, Br, CN, NH 2 , OH, CHO, COOH, oxo, C 1-4 alkyl, C 1-4 alkoxy, CONH 2 (optionally mono- or di-substituted by C 1-4 alkyl) and SO 2 NH 2 , R 2 is independently selected from C 1-6 allkyl substituted by R 3 wherein the C 1-6 alkyl chain optionally comprises one or two heteroatoms select from O; R 3 is selected from aryl, C 3-6 cycloalkyl, C 3-6 heterocyclyl and C 3-6 heteroaryl, wherein the heterocyclyl and heteroaryl rings are nitrogen containing; and wherein R 3 is optonally substituted by one or more groups selected from R 1 ; 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; R 5 is selected from any group defined for R1 and R2; R 6a and R 6b are independently selected from H or C 1-4 alkyl; R 7 is independently selected from F, CI, Br, CN, NH 2 , OH, CHO, COOH, oxo, C 1-4 alkyl, C 1-4 alkoxy, CONH 2 (optionally mono- or di-substituted by C 1-4 alkyl) and SO 2 NH 2 , Q 1 , Q 2 and Q 3 are independently selected from H or any group defined for R 1 and R 2 ; or Q 1 and Q 2 or Q 2 and Q 3 together form a C 5-6 heteroaryl or C 5-6 heterocylclic ring; optionally containing one or two heteroatoms selected from N and O optionally substituted by any group selected from R 5 ; Z is selected from linear C 2-3 alkylene; X 3 is O; X 4 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 X 4 is optionally substituted by one or two oxo moieties and is optionally substituted by one or more groups selected from R 7 ; with the proviso that: (i) when X 4 is phenyl then Q 1 and Q 2 or Q 2 and Q 3 -together form an optionally substituted heteroaryl or heterocylclic ring as defined above; and (ii) when Q 1 , Q 2 and Q 3 are independently selected from H or any group defined for R 1 and R 2 then X 4 is not phenyl except when R 2 is C 1-5 alkyl substituted by R 3 wherein R 3 is C 3-6 heterocyclyl as defined above.

Abstract translation: 式（I）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R 1独立地选自F，Cl，Br，CN，NH 2，OH，CHO，COOH，氧代， C 1-4烷基，C 1-4烷氧基，CONH 2（任选被C 1-4烷基单取代或二取代）和SO 2 NH 2，R 2独立地选自被R 3取代的C 1-6烷基，其中C 1-6烷基链任选地包含一个或两个选自 O; R3选自芳基，C3-6环烷基，C3-6杂环基和C3-6杂芳基，其中杂环基和杂芳基环是含氮的; 并且其中R3被一个或多个选自R 1的基团取代; n1为零或1〜2的整数; n2是1至2的整数; n1和2之和小于或等于2; R5选自对R1和R2定义的任何基团; R6a和R6b独立地选自H或C1-4烷基; R 7独立地选自F，Cl，Br，CN，NH 2，OH，CHO，COOH，氧代，C 1-4烷基，C 1-4烷氧基，CONH 2（任选被C 1-4烷基单取代或二取代）和SO 2 NH 2， Q2和Q3独立地选自H或为R1和R2定义的任何基团; 或Q1和Q2或Q2和Q3一起形成C5-6杂芳基或C5-6月桂基环; 任选地含有一个或两个选自N和O的杂原子，任选被选自R5的任何基团取代; Z选自直链C 2-3亚烷基; X3是O; X 4选自芳基，9-10元杂芳基环或9-10元杂环，其中杂芳基和杂环含有一个或多个选自N和任选另外O的杂原子，并且其中X 4任选被一个 或两个氧代部分，并且任选地被一个或多个选自R 7的基团取代; 条件是：（ⅰ）当X 4为苯基时，则Q1和Q2或Q2和Q3一起形成如上定义的任选取代的杂芳基或杂环基; 和（ii）当Q1，Q2和Q3独立地选自H或为R1和R2定义的任何基团时，则X4不是苯基，除非R2是被R3取代的C1-5烷基，其中R3是如上定义的C3-6杂环基。

公开(公告)号：WO2012004549A1

公开(公告)日：2012-01-12

申请号：PCT/GB2010/051106

申请日：2010-07-05

Applicant: THE UNIVERSITY OF NOTTINGHAM ,  MISTRY, Shailesh ,  DARAS, Etienne ,  FROMONT, Christophe ,  JADHAV, Gopal ,  FISCHER, Peter Martin ,  KELLAM, Barrie ,  HILL, Stephen John ,  BAKER, Jillian Glenda

Inventor： MISTRY, Shailesh ,  DARAS, Etienne ,  FROMONT, Christophe ,  JADHAV, Gopal ,  FISCHER, Peter Martin ,  KELLAM, Barrie ,  HILL, Stephen John ,  BAKER, Jillian Glenda

IPC: C07C275/40 ,  C07C275/28 ,  C07C235/34 ,  C07C335/20 ,  A61K31/16 ,  A61K31/17 ,  A61P9/04

CPC classification number: 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

Abstract: A compound of formula I-0, and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein Z 1 is C 1 -C 4 linear or branched alkyl or alkenyl; R 4 is selected from unsubstituted and substituted C 3 -C 8 cycloalkyl, C 1 -C 8 linear or branched alkyl, C 2-5 alkenyl, C 6 -C 10 heteroaryl or aryl, or C 3 -C 8 heterocyclyl which may be part unsaturated, and combinations thereof; is linear C 2-3 alkylene,; X 1 is selected from NH and O; X 2 is selected from unsaturated C and unsaturated S; and X 3 is selected from NH and CH 2 ; or one of X 1 and X 3 is a single bond; or X 1 is O and X 2 and X 3 together are a single bond; and R 7 is selected from oxo, F, Cl, Br, CN, NH 2 , NR 9 2 , NO 2 , CF 3 , OR 9 , COR 9 , OCOR 9 , COOR 9, NR 9 COR 9 , CONR 9 2 SO 2 NR 9 2 , NR 9 SO 2 R 9 ; and R 8 is selected from C 1-5 alkyl, C 1-5 alkoxyl, C 2-5 alkenyl or alkynyl, C 6-10 ) aryl and C 3-8 cycloalkyl and combinations thereof, which may be unsubstituted or f urther substituted by one or more F, Cl, Br, CN, NH 2 , NR 3 2 , NO 2 , CF 3 ; and R 9 is selected from H and a group R 8 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.

Abstract translation: 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; R4选自未取代和取代的C 3 -C 8环烷基，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，或可以是部分不饱和的C 3 -C 8杂环基，及其组合; 是直链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 9 2，NO 2，CF 3，OR 9，COR 9，OCOR 9，COOR 9，NR 9 COR 9，CONR 9 2 SO 2 NR 9 2，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，其可未被取代或被一个或多个F， Cl，Br，CN，NH 2，NR 3 2，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。