公开(公告)号：US08445686B2

公开(公告)日：2013-05-21

申请号：US12675430

申请日：2008-08-26

Applicant: Helmut Mack ,  Nicole Teusch ,  Bernhard K. Mueller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, Jr. ,  Dominique Bonafoux ,  Ryan Keddy ,  Adrian Donald Hobson ,  Anil Vasudevan

Inventor： Helmut Mack ,  Nicole Teusch ,  Bernhard K. Mueller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, Jr. ,  Dominique Bonafoux ,  Ryan Keddy ,  Adrian Donald Hobson ,  Anil Vasudevan

IPC: C07D211/78 ,  C07D211/72 ,  C07D211/84 ,  A61K31/44

CPC classification number: C07D401/12 ,  C07D213/56 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The present invention relates to novel 4-(4-pyridyl)-benzamides of the formula (I). The compounds I possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs). R1 and R2 are, independently of each other, hydrogen, hydroxy, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy or C1-C8-haloalkoxy; R3, R4, R5 and R6 are, independently of each other, hydrogen, hydroxy, halogen, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy, amino, C1-C8-alkylamino or di-(C1-C8-alkyl)-amino; R7 is hydrogen, C1-C8-alkyl, C1-C8-haloalkyl, aryl or aryl-C1-C8-alkyl; R8 is a group of the formula —X—W, where X is a single bond, C1-C4-alkylene or C1-C4-alkylene-O—, where the alkylene group in the three last-mentioned radicals may be linear or branched and may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or may be interrupted by an oxygen atom; and W is a cyclic radical selected from phenyl and a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups; R9 is a group of the formula —Y—Z, where Z is hydrogen, halogen, OR11, NR12R13, S(O)m—R14, phenyl which may carry 1, 2, 3 or 4 substituents R15 or a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring; and Y is linear or branched C1C4-alkylene which may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or a phenyl ring; or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring as defined above, Y can also be a single bond.

Abstract translation: 本发明涉及式（I）的新型4-（4-吡啶基） - 苯甲酰胺。 化合物I具有有价值的治疗特性，特别适用于治疗对Rho激酶（ROCK）的调节作用的疾病。 R 1和R 2彼此独立地为氢，羟基，氰基，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，C 1 -C 8 - 烷氧基或C 1 -C 8 - 卤代烷氧基; R3，R4，R5和R6彼此独立地为氢，羟基，卤素，氰基，C1-C8-烷基，C1-C8-卤代烷基，C1-C8-烷氧基，C1-C8-卤代烷氧基，氨基，C1- C 8 - 烷基氨基或二 - （C 1 -C 8 - 烷基） - 氨基; R 7是氢，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，芳基或芳基-C 1 -C 8 - 烷基; R8是式-XW的基团，其中X是单键，C1-C4-亚烷基或C1-C4-亚烷基-O-，其中三个最后提及的基团中的亚烷基可以是直链或支链的，并且可以 部分或完全卤化和/或可以被羟基取代和/或可被氧原子中断; 并且W是选自苯基和5-或6-元饱和，部分不饱和或芳族杂环的环状基团，其含有作为环成员1,2或3的选自O，S和N的杂原子以及任选的1或2个羰基 ; R9是式-YZ的基团，其中Z是氢，卤素，OR11，NR12R13，S（O）m -R14，可以带有1,2,3或4个取代基R15或5-或6-元的苯基 饱和，部分不饱和或芳族杂环; Y是可部分或完全卤化和/或可被羟基和/或苯环取代的直链或支链C 1 -C 4亚烷基; 或者Z为苯基或上述5-或6-元杂环的情况下，Y也可以是单键。

公开(公告)号：US20230158010A1

公开(公告)日：2023-05-25

申请号：US17923183

申请日：2021-05-03

Applicant: Tony S. GIBSON ,  Steve SWANN ,  Takeda Pharmaceutical Company Limited

Inventor： Tony S. GIBSON ,  Steve SWANN

IPC: A61K31/4545 ,  C07D211/58 ,  C07F9/59 ,  C07D405/14 ,  C07D405/12 ,  A61K31/4468 ,  A61K31/675 ,  A61K31/4525

CPC classification number: A61K31/4545 ,  C07D211/58 ,  C07F9/59 ,  C07D405/14 ,  C07D405/12 ,  A61K31/4468 ,  A61K31/675 ,  A61K31/4525

Abstract: Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein m, R1, R2, R3, R4, R5, R6, X1, X2, X3 and X4 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with the 5-HT4 receptor.

公开(公告)号：US20100273828A1

公开(公告)日：2010-10-28

申请号：US12675430

申请日：2008-08-26

Applicant: Helmut Mack ,  Nicole Teusch ,  Bernhard K. Müller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, JR. ,  Anil Vasudevan

Inventor： Helmut Mack ,  Nicole Teusch ,  Bernhard K. Müller ,  Wilfried Hornberger ,  Michael F. Jarvis ,  Daryl Sauer ,  Steve Swann, JR. ,  Anil Vasudevan

IPC: A61K31/4545 ,  A61K31/444 ,  A61K31/4439 ,  A61K31/44 ,  C07D401/02 ,  C07D213/56 ,  A61P25/16 ,  A61K9/00 ,  A61P35/00 ,  A61P11/06 ,  A61P25/00 ,  A61P25/28

CPC classification number: C07D401/12 ,  C07D213/56 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The present invention relates to novel 4-(4-pyridyl)-benzamides of the formula (I). The compounds I possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs). R1 and R2 are, independently of each other, hydrogen, hydroxy, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy or C1-C8-haloalkoxy; R3, R4, R5 and R6 are, independently of each other, hydrogen, hydroxy, halogen, cyano, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy, amino, C1-C8-alkylamino or di-(C1-C8-alkyl)-amino; R7 is hydrogen, C1-C8-alkyl, C1-C8-haloalkyl, aryl or aryl-C1-C8-alkyl; R8 is a group of the formula —X—W, where X is a single bond, C1-C4-alkylene or C1-C4-alkylene-O—, where the alkylene group in the three last-mentioned radicals may be linear or branched and may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or may be interrupted by an oxygen atom; and W is a cyclic radical selected from phenyl and a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups; R9 is a group of the formula —Y—Z, where Z is hydrogen, halogen, OR11, NR12R13, S(O)m—R14, phenyl which may carry 1, 2, 3 or 4 substituents R15 or a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring; and Y is linear or branched C1C4-alkylene which may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or a phenyl ring; or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring as defined above, Y can also be a single bond.

Abstract translation: 本发明涉及式（I）的新型4-（4-吡啶基） - 苯甲酰胺。 化合物I具有有价值的治疗特性，特别适用于治疗对Rho激酶（ROCK）的调节作用的疾病。 R 1和R 2彼此独立地为氢，羟基，氰基，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，C 1 -C 8 - 烷氧基或C 1 -C 8 - 卤代烷氧基; R3，R4，R5和R6彼此独立地为氢，羟基，卤素，氰基，C1-C8-烷基，C1-C8-卤代烷基，C1-C8-烷氧基，C1-C8-卤代烷氧基，氨基，C1- C 8 - 烷基氨基或二 - （C 1 -C 8 - 烷基） - 氨基; R 7是氢，C 1 -C 8 - 烷基，C 1 -C 8 - 卤代烷基，芳基或芳基-C 1 -C 8 - 烷基; R8是式-X-W的基团，其中X是单键，C1-C4-亚烷基或C1-C4-亚烷基-O-，其中三个最后提到的基团中的亚烷基可以是直链或支链 并且可以部分或完全卤化和/或可以被羟基取代和/或可以被氧原子中断; 并且W是选自苯基和5-或6-元饱和，部分不饱和或芳族杂环的环状基团，其含有作为环成员1,2或3的选自O，S和N的杂原子以及任选的1或2个羰基 ; R 9是式-Y-Z的基团，其中Z是氢，卤素，OR 11，NR 12 R 13，S（O）m -R 14，可带有1,2,3或4个取代基R 15或5-或6的苯基 饱和的，部分不饱和的或芳族的杂环; Y是可部分或完全卤化和/或可被羟基和/或苯环取代的直链或支链C 1 -C 4亚烷基; 或者Z为苯基或上述5-或6-元杂环的情况下，Y也可以是单键。