公开(公告)号：US08299080B2

公开(公告)日：2012-10-30

申请号：US12448212

申请日：2007-12-12

申请人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

发明人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

IPC分类号： A61K31/495

CPC分类号： C07D487/04 ,  C07D487/14

摘要： The invention discloses quinoxaline derivatives or salts thereof having PDE9-inhibiting activity and being useful as treating agent of dysuria and the like, which are represented by the formula (I) in the formula, R1 and R2 each independently stands for hydrogen, halogen, alkyl, alkoxy, acyl, amino and the like, R3 stands for alkyl, aryl, saturated carbocyclic group, saturated heterocyclic group, acyl and the like, R4 stands for hydrogen, hydroxy, alkyl or amino, R5 and R8 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkoxy, cyano or nitro, R6 and R7 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, carbocyclic group, heterocyclic group, COR9 or SO2R9, R9 stands for hydrogen, hydroxy, alkyl, amino, pyrrolidin-1-yl, piperidin-1-yl, pyperazin-1-yl or the like, X stands for S or O, and A1, A2 and A3 each independently stands for N or C.

摘要翻译： 本发明公开了具有PDE9抑制活性的喹喔啉衍生物或其盐，可用作式（I）所示的排尿困难等的治疗剂，R 1和R 2各自独立地表示氢，卤素，烷基 烷氧基，酰基，氨基等，R3代表烷基，芳基，饱和碳环基，饱和杂环基，酰基等，R4代表氢，羟基，烷基或氨基，R5和R8各自独立代表氢， 卤素，烷基，烯基，烷氧基，氰基或硝基，R6和R7各自独立地代表氢，卤素，烷基，烯基，炔基，烷氧基，氰基，氨基，碳环基，杂环基，COR9或SO2R9，R9代表氢， 羟基，烷基，氨基，吡咯烷-1-基，哌啶-1-基，哒嗪-1-基等，X表示S或O，并且，A1，A2和A3各自独立地表示N或C.

公开(公告)号：US20100048556A1

公开(公告)日：2010-02-25

申请号：US12448212

申请日：2007-12-12

申请人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

发明人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

IPC分类号： A61K31/5377 ,  C07D471/04 ,  C07D413/02 ,  A61K31/5025 ,  A61P9/10 ,  A61P13/10 ,  A61P13/12

CPC分类号： C07D487/04 ,  C07D487/14

摘要： The invention discloses quinoxaline derivatives or salts thereof having PDE9-inhibiting activity and being useful as treating agent of dysuria and the like, which are represented by the formula (I) in the formula, R1 and R2 each independently stands for hydrogen, halogen, alkyl, alkoxy, acyl, amino and the like, R3 stands for alkyl, aryl, saturated carbocyclic group, saturated heterocyclic group, acyl and the like, R4 stands for hydrogen, hydroxy, alkyl or amino, R5 and R8 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkoxy, cyano or nitro, R6 and R7 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, carbocyclic group, heterocyclic group, COR9 or SO2R9, R9 stands for hydrogen, hydroxy, alkyl, amino, pyrrolidin-1-yl, piperidin-1-yl, pyperazin-1-yl or the like, X stands for S or O, and A1, A2 and A3 each independently stands for N or C.

摘要翻译： 本发明公开了具有PDE9抑制活性的喹喔啉衍生物或其盐，可用作式（I）所示的排尿困难等的治疗剂，R 1和R 2各自独立地表示氢，卤素，烷基 烷氧基，酰基，氨基等，R3代表烷基，芳基，饱和碳环基，饱和杂环基，酰基等，R4代表氢，羟基，烷基或氨基，R5和R8各自独立代表氢， 卤素，烷基，烯基，烷氧基，氰基或硝基，R6和R7各自独立地代表氢，卤素，烷基，烯基，炔基，烷氧基，氰基，氨基，碳环基，杂环基，COR9或SO2R9，R9代表氢， 羟基，烷基，氨基，吡咯烷-1-基，哌啶-1-基，哒嗪-1-基等，X表示S或O，并且，A1，A2和A3各自独立地表示N或C.

公开(公告)号：US08829000B2

公开(公告)日：2014-09-09

申请号：US13617683

申请日：2012-09-14

申请人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

发明人： Makoto Okada ,  Shuichiro Sato ,  Kenji Kawade ,  Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi

IPC分类号： A61K31/4985 ,  C07D487/04 ,  C07D487/14

CPC分类号： C07D487/04 ,  C07D487/14

摘要： The invention discloses quinoxaline derivatives or salts thereof having PDE9-inhibiting activity and being useful as treating agent of dysuria and the like, which are represented by the formula (I) in the formula, R1 and R2 each independently stands for hydrogen, halogen, alkyl, alkoxy, acyl, amino and the like, R3 stands for alkyl, aryl, saturated carbocyclic group, saturated heterocyclic group, acyl and the like, R4 stands for hydrogen, hydroxy, alkyl or amino, R5 and R8 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkoxy, cyano or nitro, R6 and R7 each independently stands for hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, amino, carbocyclic group, heterocyclic group, COR9 or SO2R9, R9 stands for hydrogen, hydroxy, alkyl, amino, pyrrolidin-1-yl, piperidin-1-yl, pyperazin-1-yl or the like, X stands for S or O, and A1, A2 and A3 each independently stands for N or C.

摘要翻译： 本发明公开了具有PDE9抑制活性的喹喔啉衍生物或其盐，可用作式（I）所示的排尿困难等的治疗剂，R 1和R 2各自独立地表示氢，卤素，烷基 烷氧基，酰基，氨基等，R3代表烷基，芳基，饱和碳环基，饱和杂环基，酰基等，R4代表氢，羟基，烷基或氨基，R5和R8各自独立代表氢， 卤素，烷基，烯基，烷氧基，氰基或硝基，R6和R7各自独立地代表氢，卤素，烷基，烯基，炔基，烷氧基，氰基，氨基，碳环基，杂环基，COR9或SO2R9，R9代表氢， 羟基，烷基，氨基，吡咯烷-1-基，哌啶-1-基，哒嗪-1-基等，X表示S或O，并且，A1，A2和A3各自独立地表示N或C.

公开(公告)号：US20100113484A1

公开(公告)日：2010-05-06

申请号：US12448217

申请日：2007-12-12

申请人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

发明人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

IPC分类号： A61K31/519 ,  C07D495/04 ,  A61P13/00 ,  A61P13/10

CPC分类号： C07D487/04 ,  A61K31/4985 ,  A61K31/519 ,  C07D495/04

摘要： Disclosed is a treating agent of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria in benign prostatic hyperplasia or urolithiasis, which comprises a compound having PDE9-inhibiting activity as the active ingredient.

摘要翻译： 本发明涉及膀胱过度活动症，尿频尿失禁，良性前列腺增生或尿石症中的排尿困难的治疗剂，其包含具有PDE9抑制活性的化合物作为活性成分。

公开(公告)号：US08293754B2

公开(公告)日：2012-10-23

申请号：US11922233

申请日：2006-06-13

申请人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

发明人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

IPC分类号： C07D495/04 ,  A61K31/519 ,  A61P25/28

CPC分类号： C07D495/04

摘要： This invention provides thienopyrimidine derivatives of the formula, wherein R1 stands for hydrogen atom, an alkyl group or the like; R2 stands for a hydrogen atom, an alkyl or amino group or the like, R3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R2 and R3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH2, CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocycylic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

摘要翻译： 本发明提供下式的噻吩并嘧啶衍生物，其中R1代表氢原子，烷基等; R2表示氢原子，烷基或氨基等，R3表示烷基，烯基或烷硫基等或Y-X-基团; 或者R 2和R 3可以一起形成四亚甲基; X代表直接键或连接基团如CH 2，CH（OH），S，O，NH; Y表示取代或未取代的芳族碳环，芳香杂环，环烷基或饱和杂环基等; Z代表S或O，n为0或1〜4的整数，或其盐，对PDE9具有抑制作用，因此可用于预防或治疗膀胱过度活动症，尿频尿失禁，排尿困难 与前列腺增生，尿石症，阿尔茨海默病，慢性阻塞性肺疾病，心肌梗塞，血栓形成，糖尿病等相关。

公开(公告)号：US08377944B2

公开(公告)日：2013-02-19

申请号：US13585060

申请日：2012-08-14

申请人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

发明人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

IPC分类号： C07D495/04 ,  A61K31/519 ,  A61P25/28

CPC分类号： C07D495/04

摘要： This invention provides thienopyrimidine derivatives of the formula, wherein R1 stands for hydrogen atom, an alkyl group or the like; R2 stands for a hydrogen atom, an alkyl or amino group or the like, R3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R2 and R3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH2, CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocyclic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

摘要翻译： 本发明提供下式的噻吩并嘧啶衍生物，其中R1代表氢原子，烷基等; R2表示氢原子，烷基或氨基等，R3表示烷基，烯基或烷硫基等或Y-X-基团; 或者R 2和R 3可以一起形成四亚甲基; X代表直接键或连接基团如CH 2，CH（OH），S，O，NH; Y代表取代或未取代的芳族碳环，芳香杂环，环烷基或饱和杂环基等; Z代表S或O，n为0或1〜4的整数，或其盐，对PDE9具有抑制作用，因此可用于预防或治疗膀胱过度活动症，尿频尿失禁，排尿困难 与前列腺增生，尿石症，阿尔茨海默病，慢性阻塞性肺疾病，心肌梗死，血栓形成，糖尿病等相关。

公开(公告)号：US20130023546A1

公开(公告)日：2013-01-24

申请号：US13585060

申请日：2012-08-14

申请人： Kotaro GOTANDA ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

发明人： Kotaro GOTANDA ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

IPC分类号： A61K31/519 ,  A61P13/08 ,  A61P13/00

CPC分类号： C07D495/04

摘要： This invention provides thienopyrimidine derivatives of the formula, wherein R1 stands for hydrogen atom, an alkyl group or the like; R2 stands for a hydrogen atom, an alkyl or amino group or the like, R3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R2 and R3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH2, CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocycylic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

摘要翻译： 本发明提供下式的噻吩并嘧啶衍生物，其中R1代表氢原子，烷基等; R2表示氢原子，烷基或氨基等，R3表示烷基，烯基或烷硫基等或Y-X-基团; 或者R 2和R 3可以一起形成四亚甲基; X代表直接键或连接基团如CH 2，CH（OH），S，O，NH; Y表示取代或未取代的芳族碳环，芳香杂环，环烷基或饱和杂环基等; Z代表S或O，n为0或1〜4的整数，或其盐，对PDE9具有抑制作用，因此可用于预防或治疗膀胱过度活动症，尿频尿失禁，排尿困难 与前列腺增生，尿石症，阿尔茨海默病，慢性阻塞性肺疾病，心肌梗塞，血栓形成，糖尿病等相关。

公开(公告)号：US20090203703A1

公开(公告)日：2009-08-13

申请号：US11922233

申请日：2006-06-13

申请人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

发明人： Kotaro Gotanda ,  Atsushi Shinbo ,  Youichi Nakano ,  Hideo Kobayashi ,  Makoto Okada ,  Akira Asagarasu

IPC分类号： A61K31/4985 ,  C07D495/04 ,  A61K31/519

CPC分类号： C07D495/04

摘要： This invention provides thienopyrimidine derivatives of the formula, wherein R1 stands for hydrogen atom, an alkyl group or the like; R2 stands for a hydrogen atom, an alkyl or amino group or the like, R3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R2 and R3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH2, CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocycylic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

摘要翻译： 本发明提供下式的噻吩并嘧啶衍生物，其中R1代表氢原子，烷基等; R2表示氢原子，烷基或氨基等，R3表示烷基，烯基或烷硫基等或Y-X-基团; 或者R 2和R 3可以一起形成四亚甲基; X代表直接键或连接基团如CH 2，CH（OH），S，O，NH; Y表示取代或未取代的芳族碳环，芳香杂环，环烷基或饱和杂环基等; Z代表S或O，n为0或1〜4的整数，或其盐，对PDE9具有抑制作用，因此可用于预防或治疗膀胱过度活动症，尿频尿失禁，排尿困难 与前列腺增生，尿石症，阿尔茨海默病，慢性阻塞性肺疾病，心肌梗死，血栓形成，糖尿病等相关。

公开(公告)号：US08101624B2

公开(公告)日：2012-01-24

申请号：US12310025

申请日：2007-07-24

申请人： Akira Asagarasu ,  Shuichiro Sato ,  Makoto Okada

发明人： Akira Asagarasu ,  Shuichiro Sato ,  Makoto Okada

IPC分类号： A61K31/517 ,  C07D401/06 ,  C07D239/88

CPC分类号： C07D239/91 ,  C07D401/06 ,  C07D409/06

摘要： The invention discloses quinazoline derivatives or salts thereof, which possess PDE9-inhibiting activity and are useful as treating agents of dysuria and the like, the derivatives being represented by the formula (I) in the formula, R1 stands for phenyl or aromatic heterocyclic group which are optionally substituted with 1-3 substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl containing 1-6 halogen atoms and C1-6 alkoxy; and n is an integer of 1-3.

摘要翻译： 本发明公开了具有PDE9抑制活性的喹唑啉衍生物或其盐，可用作排尿困难等的治疗剂，该衍生物由式中的式（I）表示，R 1表示苯基或芳族杂环基， 任选被1-3个选自卤素，C 1-6烷基，含有1-6个卤原子的C 1-6卤代烷基和C 1-6烷氧基取代的取代基取代; n为1-3的整数。

公开(公告)号：US20090318478A1

公开(公告)日：2009-12-24

申请号：US12310025

申请日：2007-07-24

申请人： Akira Asagarasu ,  Shuichiro Sato ,  Makoto Okada

发明人： Akira Asagarasu ,  Shuichiro Sato ,  Makoto Okada

IPC分类号： A61K31/517 ,  C07D239/88 ,  C07D401/06

CPC分类号： C07D239/91 ,  C07D401/06 ,  C07D409/06

摘要： The invention discloses quinazoline derivatives or salts thereof, which possess PDE9-inhibiting activity and are useful as treating agents of dysuria and the like, the derivatives being represented by the formula (I) in the formula, R1 stands for phenyl or aromatic heterocyclic group which are optionally substituted with 1-3 substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl containing 1-6 halogen atoms and C1-6 alkoxy; and n is an integer of 1-3.

摘要翻译： 本发明公开了具有PDE9抑制活性的喹唑啉衍生物或其盐，可用作排尿困难等的治疗剂，该衍生物由式中的式（I）表示，R 1表示苯基或芳族杂环基， 任选被1-3个选自卤素，C 1-6烷基，含有1-6个卤原子的C 1-6卤代烷基和C 1-6烷氧基取代的取代基取代; n为1-3的整数。