公开(公告)号：EP3318565A1

公开(公告)日：2018-05-09

申请号：EP17200940.9

申请日：2014-11-20

申请人： Pfizer Inc.

发明人： BROWN, Matthew Frank ,  CASIMIRO-GARCIA, Agustin ,  CHE, Ye ,  COE, Jotham Wadsworth ,  FLANAGAN, Mark Edward ,  GILBERT, Adam Matthew ,  HAYWARD, Matthew Merrill ,  LANGILLE, Jonathan David ,  MONTGOMERY, Justin Ian ,  TELLIEZ, Jean-Baptiste ,  THORARENSEN, Atli ,  UNWALLA, Rayomand Jal ,  TRUJILLO, John I

IPC分类号： C07D471/04 ,  C07D487/04 ,  A61K31/4375 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/10 ,  C07D498/04

摘要： The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

摘要翻译： 本发明提供药物活性的吡咯并[2,3-d]嘧啶基和吡咯并[2,3-d]吡啶基丙烯酰胺及其类似物。 这种化合物可用于抑制Janus激酶（JAK）。 本发明还涉及包含制备此类化合物的方法的组合物，以及治疗和预防由JAK介导的病症的方法。

公开(公告)号：EP3183247B1

公开(公告)日：2017-11-29

申请号：EP15766627.2

申请日：2015-08-07

申请人： Pfizer Inc.

发明人： FENSOME, Andrew ,  GOPALSAMY, Ariamala ,  GERSTENBERGER, Brian S. ,  EFREMOV, Ivan Viktorovich ,  WAN, Zhao-Kui ,  PIERCE, Betsy ,  TELLIEZ, Jean-Baptiste ,  TRUJILLO, John I ,  ZHANG, Liying ,  XING, Li ,  SAIAH, Eddine

IPC分类号： C07D401/14 ,  C07D405/14 ,  C07D403/14 ,  C07D487/08 ,  C07D519/00 ,  A61K31/506 ,  A61P35/00 ,  A61P37/00

CPC分类号： A61K31/55 ,  A61K31/506 ,  A61K45/06 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D487/08 ,  C07D519/00

摘要： or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, CF3, or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0—, and —(CRaRb)q—, where R0 is H or C1-C4 alkyl, and Ra and Rb are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, etc.; A′ is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0′, —NR0′(C═O)—, and —(CRa′Rb′)q—, where R0′ is H or C1-C4 alkyl, and Ra′ and Rb′ are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl); Z is —(CH2)h— or a bond, where one or more methylene units are optionally substituted by one or more C1-C3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R1 and R1′ are independently selected from the group consisting of hydrogen, deuterium, C1-C4 alkyl, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, halo, CN, C1-C4 alkylamino, C3-C6 cycloalkyl, etc.; R2 is selected from the group consisting of hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R3 is selected from the group consisting of hydrogen, deuterium, and amino; R4 is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, heterocycloalkyl, halo, C3-C6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C1-C6 alkyl, halo, CN, OH, alkoxy, amino, —CO2H, —(CO)NH2, —(CO)NH(C1-C6 alkyl), or —(CO)N(C1-C6 alkyl)2, and where said alkyl may be further substituted by one or more fluorine atoms; R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

公开(公告)号：EP3183247B9

公开(公告)日：2018-07-25

申请号：EP15766627.2

申请日：2015-08-07

申请人： Pfizer Inc.

发明人： FENSOME, Andrew ,  GOPALSAMY, Ariamala ,  GERSTENBERGER, Brian S. ,  EFREMOV, Ivan Viktorovich ,  WAN, Zhao-Kui ,  PIERCE, Betsy ,  TELLIEZ, Jean-Baptiste ,  TRUJILLO, John I ,  ZHANG, Liying ,  XING, Li ,  SAIAH, Eddine

IPC分类号： C07D401/14 ,  C07D405/14 ,  C07D403/14 ,  C07D487/08 ,  C07D519/00 ,  A61K31/506 ,  A61P35/00 ,  A61P37/00

CPC分类号： A61K31/55 ,  A61K31/506 ,  A61K45/06 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D487/08 ,  C07D519/00

摘要： A compound having the structure: or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, CF3, or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0—, and —(CRaRb)q—, where R0 is H or C1-C4 alkyl, and Ra and Rb are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, etc.; A′ is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0′, —NR0′(C═O)—, and —(CRa′Rb′)q—, where R0′ is H or C1-C4 alkyl, and Ra′ and Rb′ are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl); Z is —(CH2)h— or a bond, where one or more methylene units are optionally substituted by one or more C1-C3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R1 and R1′ are independently selected from the group consisting of hydrogen, deuterium, C1-C4 alkyl, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, halo, CN, C1-C4 alkylamino, C3-C6 cycloalkyl, etc.; R2 is selected from the group consisting of hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R3 is selected from the group consisting of hydrogen, deuterium, and amino; R4 is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, heterocycloalkyl, halo, C3-C6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C1-C6 alkyl, halo, CN, OH, alkoxy, amino, —CO2H, —(CO)NH2, —(CO)NH(C1-C6 alkyl), or —(CO)N(C1-C6 alkyl)2, and where said alkyl may be further substituted by one or more fluorine atoms; R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

公开(公告)号：EP3183247A1

公开(公告)日：2017-06-28

申请号：EP15766627.2

申请日：2015-08-07

申请人： Pfizer Inc.

发明人： FENSOME, Andrew ,  GOPALSAMY, Ariamala ,  GERSTENBERGER, Brian S. ,  EFREMOV, Ivan Viktorovich ,  WAN, Zhao-Kui ,  PIERCE, Betsy ,  TELLIEZ, Jean-Baptiste ,  TRUJILLO, John I ,  ZHANG, Liying ,  XING, Li ,  SAIAH, Eddine

IPC分类号： C07D401/14 ,  C07D405/14 ,  C07D403/14 ,  C07D487/08 ,  C07D519/00 ,  A61K31/506 ,  A61P35/00 ,  A61P37/00

CPC分类号： A61K31/55 ,  A61K31/506 ,  A61K45/06 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D487/08 ,  C07D519/00

摘要： or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, CF3, or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0—, and —(CRaRb)q—, where R0 is H or C1-C4 alkyl, and Ra and Rb are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, etc.; A′ is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0′, —NR0′(C═O)—, and —(CRa′Rb′)q—, where R0′ is H or C1-C4 alkyl, and Ra′ and Rb′ are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl); Z is —(CH2)h— or a bond, where one or more methylene units are optionally substituted by one or more C1-C3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R1 and R1′ are independently selected from the group consisting of hydrogen, deuterium, C1-C4 alkyl, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, halo, CN, C1-C4 alkylamino, C3-C6 cycloalkyl, etc.; R2 is selected from the group consisting of hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R3 is selected from the group consisting of hydrogen, deuterium, and amino; R4 is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, heterocycloalkyl, halo, C3-C6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C1-C6 alkyl, halo, CN, OH, alkoxy, amino, —CO2H, —(CO)NH2, —(CO)NH(C1-C6 alkyl), or —(CO)N(C1-C6 alkyl)2, and where said alkyl may be further substituted by one or more fluorine atoms; R5 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

摘要翻译： 具有以下结构的化合物或其药学上可接受的盐，其中X是N或CR，其中R是氢，氘，C 1 -C 4烷基，C 1 -C 4烷氧基，C 3 -C 6环烷基，芳基，杂芳基， C6烷基），CN，氨基，烷基氨基，二烷基氨基，CF3或羟基; A选自键，C = O，-SO 2 - ， - （C = O）NR 0 - 和 - （CR a R b）q - ，其中R 0为H或C 1 -C 4烷基，并且R a和R b 氘，C1-C6烷基，C3-C6环烷基，芳基，芳基（C1-C6烷基），杂芳基，（C1-C6烷基）杂芳基等。 A'选自键，C = O，-SO 2 - ， - （C = O）NR 0'，-NR 0'（C = O） - 和 - （CR a'R b'）q-组成的组， 其中R 0'为H或C 1 -C 4烷基，并且R a'和R b'独立地为氢，氘，C 1 -C 6烷基，C 3 -C 6环烷基，芳基，芳基（C 1 -C 6烷基） ）杂芳基，杂芳基（C 1 -C 6烷基）和杂环（C 1 -C 6烷基）; Z为 - （CH 2）h - 或键，其中一个或多个亚甲基单元任选被一个或多个C 1 -C 3烷基，CN，OH，甲氧基或卤素取代，并且其中所述烷基可被一个或多个 氟原子; R1和R1'独立地选自氢，氘，C1-C4烷基，C3-C6环烷基，芳基，杂芳基，芳基（C1-C6烷基），CN等，其中所述烷基，芳基，环烷基 杂环或杂芳基进一步任选被一个或多个选自C 1 -C 6烷基，卤素，CN，C 1 -C 4烷基氨基，C 3 -C 6环烷基等的取代基取代; R 2选自氢，氘，C 1 -C 6烷基，C 3 -C 6环烷基，卤素和氰基，其中所述烷基可以被一个或多个氟原子取代; R3选自氢，氘和氨基; R 4是单环或双环芳基或单环或双环杂芳基，其中所述芳基或杂芳基任选被一个或多个选自C 1 -C 6烷基，杂环烷基，卤代，C 3 -C 6环烷基等的取代基取代，其中所述烷基 （CO）NH（C 1 -C 6烷基）， - （C 1 -C 6烷基）， - 或 - （CO）N（C 1 -C 6烷基）2，并且其中所述烷基可以进一步被一个或多个氟原子取代; R5独立地选自氢，C1-C6烷基，C1-C6烷氧基和羟基; h是1,2或3; j和k独立地为0,1,2或3; m和n独立地为0,1或2; 并且q是0,1或2.还提供了作为Janus激酶抑制剂和含有本发明化合物和其他治疗剂组合的药物组合物的治疗方法。

公开(公告)号：EP3077395B1

公开(公告)日：2017-11-15

申请号：EP14816404.9

申请日：2014-11-20

申请人： Pfizer Inc.

发明人： BROWN, Matthew Frank ,  CASIMIRO-GARCIA, Agustin ,  CHE, Ye ,  COE, Jotham Wadsworth ,  FLANAGAN, Mark Edward ,  GILBERT, Adam Matthew ,  HAYWARD, Matthew Merrill ,  LANGILLE, Jonathan David ,  MONTGOMERY, Justin Ian ,  TELLIEZ, Jean-Baptiste ,  THORARENSEN, Atli ,  UNWALLA, Rayomand Jal ,  TRUJILLO, John I

IPC分类号： A61P35/00 ,  A61K31/4375 ,  C07D471/04 ,  C07D487/04 ,  C07D471/08 ,  C07D487/10 ,  C07D498/04

CPC分类号： C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/10 ,  C07D498/04

公开(公告)号：EP3077395A1

公开(公告)日：2016-10-12

申请号：EP14816404.9

申请日：2014-11-20

申请人： Pfizer Inc.

发明人： BROWN, Matthew Frank ,  CASIMIRO-GARCIA, Agustin ,  CHE, Ye ,  COE, Jotham Wadsworth ,  FLANAGAN, Mark Edward ,  GILBERT, Adam Matthew ,  HAYWARD, Matthew Merrill ,  LANGILLE, Jonathan David ,  MONTGOMERY, Justin Ian ,  TELLIEZ, Jean-Baptiste ,  THORARENSEN, Atli ,  UNWALLA, Rayomand Jal ,  TRUJILLO, John I

IPC分类号： C07D471/04 ,  C07D487/04 ,  A61K31/4375 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/10 ,  C07D498/04

摘要： The present invention provides pharmaceutically active pyrrolo[2,3- d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

摘要翻译： 本发明提供药学活性吡咯并[2,3-d]嘧啶基和吡咯并[2,3-d]吡啶基丙烯酰胺及其类似物。 这些化合物可用于抑制Janus Kinase（JAK）。 本发明还涉及包含制备这些化合物的方法的组合物，以及用于治疗和预防由JAK介导的病症的方法。