公开(公告)号：US08592444B2

公开(公告)日：2013-11-26

申请号：US12988197

申请日：2009-04-14

申请人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

发明人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

IPC分类号： C07D401/04 ,  A61K31/438

CPC分类号： C07D498/10 ,  A61K31/438 ,  C07D471/10 ,  C07D491/107 ,  Y02A50/409 ,  Y02A50/411

摘要： This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R3; (SO2)R4; cycloalkyl; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C═R11; and R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

摘要翻译： 本发明涉及根据通式（I）的新的组蛋白脱乙酰酶抑制剂，其中：虚线是任选的附加键; n为0或1至4的整数; R1是氢; 任选被环烷基，芳基或杂芳基取代的C 1 -C 6烷基; （CO）R3; （SO2）R4; 环烷基 芳基; 或杂芳基; R2是任选被芳基或杂芳基取代的C 1 -C 6烷基; 芳基; 杂芳基; 或（CO）R5; X是CH 2，氧或NR 6; Y是一个键，CHR7或NR8; Z是氧，CR9R10或C = R11; R3，R4，R5，R6，R7，R8，R9，R10和R11在说明书中进一步定义; 及其药学上可接受的盐。

公开(公告)号：US20110039840A1

公开(公告)日：2011-02-17

申请号：US12988197

申请日：2009-04-14

申请人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

发明人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

IPC分类号： A61K31/537 ,  C07D491/10 ,  A61K31/438 ,  A61P35/00 ,  A61P31/18 ,  A61P25/08 ,  A61P9/10 ,  A61P37/00 ,  A61P17/06 ,  A61P35/04 ,  A61P25/16 ,  A61P25/28 ,  A61P25/18 ,  A61P33/06 ,  A61P33/02 ,  A61P31/10 ,  A61P31/12 ,  C07D498/10 ,  C07D471/10 ,  A61K31/527 ,  A61K31/506

CPC分类号： C07D498/10 ,  A61K31/438 ,  C07D471/10 ,  C07D491/107 ,  Y02A50/409 ,  Y02A50/411

摘要： This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R3; (SO2)R4; cycloalkyl; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C═R11; and R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

摘要翻译： 本发明涉及根据通式（I）的新的组蛋白脱乙酰酶抑制剂，其中：虚线是任选的附加键; n为0或1至4的整数; R1是氢; 任选被环烷基，芳基或杂芳基取代的C 1 -C 6烷基; （CO）R3; （SO2）R4; 环烷基 芳基; 或杂芳基; R2是任选被芳基或杂芳基取代的C 1 -C 6烷基; 芳基; 杂芳基; 或（CO）R5; X是CH 2，氧或NR 6; Y是一个键，CHR7或NR8; Z是氧，CR9R10或C = R11; R3，R4，R5，R6，R7，R8，R9，R10和R11在说明书中进一步定义; 及其药学上可接受的盐。

公开(公告)号：US20140080823A1

公开(公告)日：2014-03-20

申请号：US14088061

申请日：2013-11-22

申请人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

发明人： Mario Varasi ,  Florian Thaler ,  Agnese Abate ,  Giacomo Carenzi ,  Ciro Mercurio ,  Saverio Minucci

IPC分类号： C07D498/10 ,  C07D471/10 ,  C07D491/107

CPC分类号： C07D498/10 ,  A61K31/438 ,  C07D471/10 ,  C07D491/107 ,  Y02A50/409 ,  Y02A50/411

摘要： This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R3; (SO2)R4; cycloalkyl; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C═R11; and R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

摘要翻译： 本发明涉及根据通式（I）的新的组蛋白脱乙酰酶抑制剂，其中：虚线是任选的附加键; n为0或1至4的整数; R1是氢; 任选被环烷基，芳基或杂芳基取代的C 1 -C 6烷基; （CO）R3; （SO2）R4; 环烷基 芳基; 或杂芳基; R2是任选被芳基或杂芳基取代的C 1 -C 6烷基; 芳基; 杂芳基; 或（CO）R5; X是CH 2，氧或NR 6; Y是一个键，CHR7或NR8; Z是氧，CR9R10或C = R11; R3，R4，R5，R6，R7，R8，R9，R10和R11在说明书中进一步定义; 及其药学上可接受的盐。

公开(公告)号：US20120258949A1

公开(公告)日：2012-10-11

申请号：US13446861

申请日：2012-04-13

申请人： Mario Varasi ,  Florian Thaler ,  Raffaella Amici ,  Agnese Abate ,  Maria Carmela Fulco ,  Saverio Minucci ,  Ciro Mercurio

发明人： Mario Varasi ,  Florian Thaler ,  Raffaella Amici ,  Agnese Abate ,  Maria Carmela Fulco ,  Saverio Minucci ,  Ciro Mercurio

IPC分类号： A61K31/407 ,  A61K31/438 ,  A61K31/55 ,  A61K31/397 ,  C07D498/10 ,  A61K31/537 ,  A61P35/00 ,  A61P25/00 ,  A61P29/00 ,  A61P31/00 ,  A61P11/00 ,  A61P37/00 ,  A61P9/00 ,  A61P21/00 ,  A61P17/06 ,  C07D491/107

CPC分类号： A61K31/397 ,  A61K31/407 ,  A61K31/438 ,  A61K31/537 ,  A61K31/55 ,  C07D491/107 ,  C07D498/10

摘要： This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl or hetero(C2-C9)aryl; (CO)R2; (SO2)R3; C3-C8 cycloalkyl; C6-C10 aryl; or hetero(C2-C9)aryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; Y is CH2 or NR4; Z is C═R5; and R2, R3, R4, and R5 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

摘要翻译： 本发明涉及根据通式（I）的新的组蛋白脱乙酰酶抑制剂，其中：m和n独立地为0或1至4的整数; p为0或1至3的整数，条件是当p为零时，n和m不能同时为1; R是氢; 任选被C 3 -C 8环烷基，C 6 -C 10芳基或杂（C 2 -C 9）芳基取代的C 1 -C 6烷基; （CO）R2; （SO2）R3; C3-C8环烷基; C6-C10芳基; 或杂（C 2 -C 9）芳基; R1是卤素，C1-C6烷基，C1-C6卤代烷基，C1-C6烷氧基，C1-C6卤代烷氧基; Y是CH 2或NR 4; Z为C = R5; R2，R3，R4和R5如说明书中进一步定义; 及其药学上可接受的盐。

公开(公告)号：US08980877B2

公开(公告)日：2015-03-17

申请号：US13446861

申请日：2012-04-13

申请人： Mario Varasi ,  Florian Thaler ,  Raffaella Amici ,  Agnese Abate ,  Maria Carmela Fulco ,  Saverio Minucci ,  Ciro Mercurio

发明人： Mario Varasi ,  Florian Thaler ,  Raffaella Amici ,  Agnese Abate ,  Maria Carmela Fulco ,  Saverio Minucci ,  Ciro Mercurio

IPC分类号： A61K31/407 ,  A61K31/438 ,  A61K31/55 ,  C07D491/107 ,  A61K31/397 ,  A61K31/537 ,  C07D498/10

CPC分类号： A61K31/397 ,  A61K31/407 ,  A61K31/438 ,  A61K31/537 ,  A61K31/55 ,  C07D491/107 ,  C07D498/10

摘要： This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl or hetero(C2-C9)aryl; (CO)R2; (SO2)R3; C3-C8 cycloalkyl; C6-C10 aryl; or hetero(C2-C9)aryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; Y is CH2 or NR4; Z is C═R5; and R2, R3, R4, and R5 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

摘要翻译： 本发明涉及根据通式（I）的新的组蛋白脱乙酰酶抑制剂，其中：m和n独立地为0或1至4的整数; p为0或1至3的整数，条件是当p为零时，n和m不能同时为1; R是氢; 任选被C 3 -C 8环烷基，C 6 -C 10芳基或杂（C 2 -C 9）芳基取代的C 1 -C 6烷基; （CO）R2; （SO2）R3; C3-C8环烷基; C6-C10芳基; 或杂（C 2 -C 9）芳基; R1是卤素，C1-C6烷基，C1-C6卤代烷基，C1-C6烷氧基，C1-C6卤代烷氧基; Y是CH 2或NR 4; Z为C = R5; R2，R3，R4和R5如说明书中进一步定义; 及其药学上可接受的盐。