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1. 发明申请

WO2019035927A1 MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE 审中-公开
公开(公告)号：WO2019035927A1
公开(公告)日：2019-02-21
申请号：PCT/US2018/000196
申请日：2018-08-15
申请人： ABBVIE INC. , ABBVIE DEUTSCHLAND GMBH & CO. KG , BRAJE, Wilfried , DOHERTY, George , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke , TESKE, Jessc , WENDT, Michael , BRADY, Patrick , WANG, Xilu , PENNING, Thomas , MICHAELIDES, Michael
发明人： BRAJE, Wilfried , DOHERTY, George , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke , TESKE, Jessc , WENDT, Michael , BRADY, Patrick , WANG, Xilu , PENNING, Thomas , MICHAELIDES, Michael
IPC分类号： A61K31/395 , A61P35/00 , C07D515/22
摘要： The present disclosure provides for compounds of Formula (I) wherein A 2 , A 3 , A 4 , A 6 , A 7 , A 8 , A 15 , R A , R 5 , R 9 , R 10A , R 10B , R 11 , R 12 , R 13 , R 14 , R 16 , W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

3. 发明申请

WO2019035914A1 MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE 审中-公开
公开(公告)号：WO2019035914A1
公开(公告)日：2019-02-21
申请号：PCT/US2018/000183
申请日：2018-08-15
申请人： ABBVIE INC. , ABBVIE DEUTSCHLAND GMBH & CO. KG , BRADY, Patrick , BRAJE, Wilfried , DAI, Yujia , DOHERTY, George , GONG, Jane , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , RISI, Roberto , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , YU, Yiyun , ZHU, Guidong , PENNING, Thomas , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke , POTIN, Dominique , GUILLIER, Fabrice
发明人： BRADY, Patrick , BRAJE, Wilfried , DAI, Yujia , DOHERTY, George , GONG, Jane , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , RISI, Roberto , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , YU, Yiyun , ZHU, Guidong , PENNING, Thomas , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke , POTIN, Dominique , GUILLIER, Fabrice
IPC分类号： A61K31/395 , A61P35/00 , C07D515/22
摘要： The present disclosure provides for compounds of Formula (I) wherein A 2 , A 3 , A 4 , A 6 , A 7 , A 8 , A 15 , R A , R 5 , R 9 , R 10A , R 10B , R 11 , R 12 , R 13 , R 14 , R 16 , W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

4. 发明申请

WO2019035911A1 MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE 审中-公开
公开(公告)号：WO2019035911A1
公开(公告)日：2019-02-21
申请号：PCT/US2018/000180
申请日：2018-08-15
申请人： ABBVIE INC. , ABBVIE DEUTSCHLAND GMBH & CO. KG , BRAJE, Wilfried , DOHERTY, George , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , PENNING, Thomas , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke
发明人： BRAJE, Wilfried , DOHERTY, George , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-Fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , PENNING, Thomas , LAI, Chunqui , KLING, Andreas , POHLKI, Frauke
IPC分类号： A61K31/395 , A61P35/00 , C07D515/22
摘要： The present disclosure provides for compounds of formula (I), wherein A 2 , A 3 , A 4 , A 6 , A 7 , A 8 , A 15 , R A , R 5 , R 9 , R 10A , R 10B , R 11 , R 12 , R 13 , R 14 , R 16 , W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of formula (I).

5. 发明申请

WO2019035899A1 MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE 审中-公开
公开(公告)号：WO2019035899A1
公开(公告)日：2019-02-21
申请号：PCT/US2018/000167
申请日：2018-08-15
申请人： ABBVIE INC. , ABBVIE DEUTSCHLAND GMBH & CO. KG , BRADY, Patrick , BRAJE, Wilfried , DAI, Yujia , DOHERTY, George , GONG, Jane , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , RISI, Roberto , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , YU, Yiyun , ZHU, Guidong , PENNING, Thomas , LAI, Chunqiu
发明人： BRADY, Patrick , BRAJE, Wilfried , DAI, Yujia , DOHERTY, George , GONG, Jane , JANTOS, Katja , JI, Cheng , JUDD, Andrew , KUNZER, Aaron , MASTRACCHIO, Anthony , RISI, Roberto , SONG, Xiaohong , SOUERS, Andrew , SULLIVAN, Gerard , TAO, Zhi-fu , TESKE, Jesse , WANG, Xilu , WENDT, Michael , YU, Yiyun , ZHU, Guidong , PENNING, Thomas , LAI, Chunqiu
IPC分类号： A61K31/395 , A61P35/00 , C07D515/22
摘要： The present disclosure provides for compounds of Formula (I) wherein A 2 , A 3 , A 4 , A 6 , A 7 , A 8 , A 15 , R A , R 5 , R 9 , R 10A , R 10B , R 11 , R 12 , R 13 , R 14 , R 16 , W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

6. 发明申请

WO2015091931A1 OXINDOLE DERIVATIVES CARRYING A PIPERIDYL-SUBSTITUTED AZETIDINYL SUBSTITUENT AND USE THEREOF FOR TREATING VASOPRESSINE-RELATED DISEASES 审中-公开
标题翻译：携带哌啶取代的亚胺基取代基的氧化衍生物及其用于治疗类风湿关节疾病的用途
公开(公告)号：WO2015091931A1
公开(公告)日：2015-06-25
申请号：PCT/EP2014/078699
申请日：2014-12-19
申请人： ABBVIE DEUTSCHLAND GMBH & CO. KG , ABBVIE INC.
发明人： GENESTE, Hervé , HORNBERGER, Wilfried , HUTCHINS, Charles W. , JANTOS, Katja , KLING, Andreas , LAPLANCHE, Loic , VAN GAALEN, Marcel
IPC分类号： C07D401/14 , C07D401/04 , A61K31/444 , A61P25/24 , A61P3/10
CPC分类号： C07D401/14 , C07B59/002 , C07B2200/05 , C07D401/04 , C07D405/14 , C07D491/107
摘要： The present invention relates to novel substituted oxindole derivatives of formula (I) wherein the variables are as defined in the claims and description; to pharmaceutical compositions comprising them, and to their use for treatment of vasopressin-related disorders.
摘要翻译：本发明涉及式（I）的新型取代的羟基吲哚衍生物，其中变量如权利要求和说明书所定义; 包含它们的药物组合物及其用于治疗加压素相关病症的用途。

7. 发明申请

WO2014079995A2 NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A 审中-公开
标题翻译：新型的磷酸二酯酶抑制剂化合物10A
公开(公告)号：WO2014079995A2
公开(公告)日：2014-05-30
申请号：PCT/EP2013/074532
申请日：2013-11-25
申请人： ABBVIE INC. , ABBVIE DEUTSCHLAND GMBH & CO. KG
发明人： GENESTE, Hervé , TURNER, Sean , OCHSE, Michael , DRESCHER, Karla , BLACK, Lawrence A. , JANTOS, Katja
IPC分类号： C07D401/14 , A61K31/4353 , A61K31/4427 , C07D401/04 , C07D401/10 , C07D471/04 , C07D487/04
CPC分类号： C07D401/14 , C07D401/04 , C07D401/10 , C07D471/04 , C07D487/04
摘要： The present invention relates to compounds of the formula I and their salts etc. which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders wherein Y 1 and Y 2 are adjacent atoms in Het 1 , which are independently selected from the group consisting of carbon and nitrogen; k is 0, 1, 2 or 3; Het 1 is a bivalent monocyclic 5- or 6-membered heteroaromatic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N-R a as ring members, or a bivalent fused bicyclic 8-, 9- or 10-membered heteroaromatic radical, having 1, 2, 3 or 4 heteroatoms or heteroatom moieties selected from O, S, N and N-R a as ring members; Het 2 is inter alia monocyclic 5- or 6-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N-R 1a as ring members, Cyc is inter alia optionally substituted monocyclic 5- or 6-membered hetaryl or optionally substituted fused 8-, 9- or 10-membered bicyclic hetaryl; Ar is optionally substituted phenylene or optionally substituted bivalent 6-membered hetaryl; R is attached to a carbon atom of Het 1 and inter alia - halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl etc.
摘要翻译：本发明涉及作为磷酸二酯酶10A型抑制剂的式I化合物及其盐等，并涉及它们在制备药物中的应用，因此适用于治疗或控制选自神经障碍和精神障碍的医学病症，用于改善与这种病症相关的症状，以及用于降低这种病症的风险，其中Y 1和Y 2是相邻的原子 Het 1，它们独立地选自由碳和氮组成的组; k是0,1,2或3; Het 1是具有1,2或3个选自O，S，N和NR a的杂原子或杂原子部分的二价单环5-或6-元杂芳族基团，其为环成员或具有1,2,3或4个选自O，S，N和NR a的杂原子或杂原子部分的二价稠合双环8,9或10元杂芳族基团作为戒指成员; Het 2尤其是单环5-或6-元杂芳基，其具有1,2或3个选自O，S，N和NR 1a的杂原子或杂原子部分作为环 Cyc特别是任选取代的单环5-或6-元杂芳基或任选取代的稠合的8-，9-或10-元双环杂芳基; Ar是任选取代的亚苯基或任选取代的二价6-元杂芳基; R连接到Het 1 1的碳原子上，尤其是 - 卤素，C 1 -C 6 - 烷基，C≡2 C 6 -C 6 - 烯基，C 2 -C 6 - 炔基，C 1 -C 6 - C 1-6 - 烷氧基，C 1 -C 6 - 氟代烷基，C 1 -C 6 - 烷氧基，C 1 -C 6 - C 1-3 - 烷氧基，C 3-6 - 环烷基等。

8. 发明申请

WO2014140086A1 NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A 审中-公开
标题翻译：磷酸二酯酶类型10A的新型抑制剂化合物
公开(公告)号：WO2014140086A1
公开(公告)日：2014-09-18
申请号：PCT/EP2014/054810
申请日：2014-03-12
申请人： ABBVIE DEUTSCHLAND GMBH & CO. KG , ABBVIE INC.
发明人： JANTOS, Katja , OCHSE, Michael , GENESTE, Hervé , FROGGETT, Jayne , JAKOB, Clarissa , DRESCHER, Karla , DINGES, Jürgen
IPC分类号： C07D495/04 , A61K31/5025 , A61P25/00
CPC分类号： C07D495/04
摘要： The present invention relates to compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof: (I). In formula I the variables X 1 is CH or N, X 2 is O or S and where R 1 , R 2 , R 3 , R 4 and Q are as defined in the claims. The compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type 10A. Thus, the invention also relates to the use of the compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.
摘要翻译：本发明涉及式I化合物，其N-氧化物，互变异构体，其前药及其药学上可接受的盐：（I）。在式I中，变量X1是CH或N，X2是O或S，其中R1，R2，R3，R4和Q如权利要求中所定义。式I化合物，N-氧化物，互变异构体，其前药和药学上可接受的盐是10A型磷酸二酯酶的抑制剂。因此，本发明还涉及式I化合物，N-氧化物，互变异构体，前药和其药学上可接受的盐在制备药物中的用途，因此其适用于治疗或控制医学病症选自神经障碍和精神障碍，用于改善与这种障碍相关的症状并降低这种障碍的风险。

9. 发明申请

WO2010128102A1 CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS 审中-公开
标题翻译：羧酰胺化合物及其作为钙蛋白酶抑制剂的用途
公开(公告)号：WO2010128102A1
公开(公告)日：2010-11-11
申请号：PCT/EP2010/056166
申请日：2010-05-06
申请人： ABBOTT GMBH & CO. KG , MACK, Helmut , KLING, Andreas , JANTOS, Katja , MOELLER, Achim , HORNBERGER, Wilfried , HUTCHINS, Charles, W.
发明人： MACK, Helmut , KLING, Andreas , JANTOS, Katja , MOELLER, Achim , HORNBERGER, Wilfried , HUTCHINS, Charles, W.
IPC分类号： C07D207/26 , C07D211/76 , C07D233/34 , C07D239/10 , A61K31/4412
CPC分类号： C07D207/22 , C07D207/26 , C07D207/28 , C07D211/76 , C07D211/78 , C07D213/81 , C07D233/32 , C07D233/34 , C07D239/10 , C07D275/03 , C07D401/06 , C07D401/12 , C07D405/12 , C07D409/12 , C07D417/12
摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R 1 , R 2 , R 3a , R 3b , R 4 , Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula (Ia) and (Ib) in which R 1 , r, R 2b , R 3a , R 3b , R 4 , Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH 2 -CH 2 , CH 2 -CH 2 -CH 2 , N(R y# )-CH2, N(R y# )-CH 2 -CH 2 or CH=CH-CH=, each optionally having 1 or 2 H-atoms replaced with identical or different radicals R y , wherein R y and R y# have the meanings mentioned in the claims.
摘要翻译：本发明涉及新的羧酰胺化合物及其用于制备药物的用途。羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。羧酰胺化合物是通式（I）的化合物，其中R 1，R 2，R 3a，R 3b，R 4，Q，Y，A和X具有权利要求书和描述中所述的含义，其互变异构体和药学上合适的盐它们。特别地，化合物具有通式（Ia）和（Ib），其中R1，r，R2b，R3a，R3b，R4，Y和X具有权利要求中提及的含义，包括其互变异构体和药学上合适的盐它们。在这些化合物中，优选其中Y为CH2-CH2，CH2-CH2-CH2，N（Ry＃）-CH2，N（Ry＃）-CH2-CH2或CH = CH-CH =，各自任选具有1 或2个H原子被相同或不同的基团Ry取代，其中Ry和Ry＃具有权利要求中提及的含义。

10. 发明申请

WO2012076639A1 CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS V 审中-公开
标题翻译：羧酰胺化合物及其作为钙抑制剂V
公开(公告)号：WO2012076639A1
公开(公告)日：2012-06-14
申请号：PCT/EP2011/072164
申请日：2011-12-08
申请人： ABBOTT GMBH & CO. KG , ABBOTT LABORATORIES , KLING, Andreas , JANTOS, Katja , MACK, Helmut , MÖLLER, Achim , HORNBERGER, Wilfried , LAO, Yanbin , BACKFISCH, Gisela , NIJSEN, Marjoleen
发明人： KLING, Andreas , JANTOS, Katja , MACK, Helmut , MÖLLER, Achim , HORNBERGER, Wilfried , LAO, Yanbin , BACKFISCH, Gisela , NIJSEN, Marjoleen
IPC分类号： A61K31/4439 , C07D401/04 , A61P25/28
CPC分类号： C07D401/04 , A61K31/4439 , C07D401/14 , Y02A50/411
摘要： The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R 1 , R 2 , R 3 R 4 , X, m and n have the meanings mentioned in the claims and the description, the tautomers thereof, the hydrates thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein R 1 is optionally substituted benzyl or hetaryl-methyl, X is a single bond or an oxygen atom, R 2 is C 1 -C 4 - alkyl, C 1 -C 4 -haloalkyl, C 2 -C 4 -alkenyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 2 -alkyl, C 3 -C 6 -heterocycloalkyl-C 1 -C 2 -alkyl, phenyl, phenyl-C 1 -C 3 -alkyl, pyridin-2-yl-C 1 -C 3 -alkyl or CH 2 -C(O)OCH 3 ,R 3 and R 4 independently of one another are halogen, CN, CF 3 , CHF 2 , CH 2 F, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy, and m and n independently of one another are 0 or 1.
摘要翻译：本发明涉及新的羧酰胺化合物及其用于制备药物的用途。羧酰胺化合物是钙蛋白酶（钙依赖性半胱氨酸蛋白酶）的抑制剂。因此，本发明还涉及这些羧酰胺化合物用于治疗与升高的钙蛋白酶活性相关的病症的用途。羧酰胺化合物是通式（I）的化合物，其中R 1，R 2，R 3，R 4，X，m和n具有权利要求书和描述中所述的含义，其互变异构体，其水合物及其药学上合适的盐。在这些化合物中，优选其中R 1为任选取代的苄基或杂芳基 - 甲基，X为单键或氧原子，R 2为C 1 -C 4烷基，C 1 -C 4卤代烷基，C 2 -C 4 - 烯基，C 3 -C 6 环烷基，C 3 -C 6 - 环烷基-C 1 -C 2 - 烷基，C 3 -C 6 - 杂环烷基-C 1 -C 2烷基，苯基，苯基-C 1 -C 3 - 烷基，吡啶-2-基-C 1 -C 3 - 烷基或CH 2 -C（O）OCH 3，R 3和R 4彼此独立地是卤素，CN，CF 3，CHF 2，CH 2 F，C 1 -C 2 - 烷基或C 1 -C 2 - 烷氧基，m和n彼此独立地为0或1。

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