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：US06667325B1

公开(公告)日：2003-12-23

申请号：US09980579

申请日：2001-12-03

申请人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

发明人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

IPC分类号： C07D40104

CPC分类号： C07D231/12 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/4725 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  Y02A50/411

摘要： Substituted pyrazole compounds represented by formula (I), or salts thereof are disclosed, wherein R1 is —CH(OH)—CH(R4)—(A)n—Y, —CH2—CH(R4)—(A)n—Y, —CO—B1—A—Y or the like (wherein A is a lower alkylene; Y is an aryl group which may be substituted, for example, by halogen, or the like; R4 is a hydrogen atom or a lower alkyl group; B1 is —CH(R4)— or —N(R4)—; and n is 0 or 1); R2 is a hydrogen atom, a lower alkyl group which may be substituted by hydroxyl or the like, or an aralkyl group; R3 is a phenyl group which may be substituted by halogen or the like, or a pyridyl group; and Q is a pyridyl or quinolyl group. These substituted pyrazole compounds or their salts have an excellent p38MAP kinase inhibiting effect and are hence useful in the prevention or treatment of tumor necrosis factor &agr;-related diseases, interleukin 1-related diseases, interleukin 6-related diseases or cyclooxygenase II-related diseases.

摘要翻译： 公开了由式（I）表示的取代的吡唑化合物或其盐，其中R 1是-CH（OH）-CH（R 4） - （A）n Y，-CH 2 -CH（R 4） ） - （A）nY，-CO-B 1 -AY等（其中A是低级亚烷基; Y是可以被卤素取代的芳基等; R 4 >是氢原子或低级烷基; B 1是-CH（R 4） - 或-N（R 4） - ，n是0或1）; R 2是氢原子，可以被羟基等取代的低级烷基或芳烷基; R 3是可被卤素等取代的苯基或吡啶基; Q为吡啶基或喹啉基。 这些取代的吡唑化合物或其盐具有优异的p38MAP激酶抑制作用，因此可用于预防或治疗肿瘤坏死因子α相关疾病，白细胞介素1相关疾病，白介素6相关疾病或环加氧酶II相关疾病。

公开(公告)号：US06511997B1

公开(公告)日：2003-01-28

申请号：US09869051

申请日：2001-06-22

申请人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

发明人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

IPC分类号： A61K314409

CPC分类号： C07D401/04 ,  C07D405/14

摘要： Aminopyrazole derivatives represented by formula (I), or salts thereof, wherein X1 and X2 are each a hydrogen atom or a halogen atom, or X1 and X2 may be united together to form a lower alkylenedioxy group, Q is a pyridyl group or a quinolyl group, R1 is a hydrogen atom, a substituted or unsubstituted lower alkyl or aryl group, R2 is a hydrogen atom, a lower alkyl group, or an aralkyl group, and R3 represents a hydrogen atom, an organic sulfonyl group, or —C(═Y)—R4 in which R4 is a hydrogen atom or an organic residue and Y is an oxygen or sulfur atom, provided that, when R3 is a hydrogen atom, R1 is a group other than a hydrogen atom and R2 is a hydrogen atom. These amimopyrazole derivatives or their salts have excellent p38MAP kinase inhibiting activities and are hence useful in the prevention or treatment of diseases associated with tumor necrosis sis factor &agr;, interleukin 1, interleukin 6 or cyclooxygenase II.

摘要翻译： 式（I）表示的氨基吡唑衍生物或其盐，其中X 1和X 2各自为氢原子或卤素原子，或者X 1和X 2可以一起结合形成低级亚烷基二氧基，Q是吡啶基或喹啉基 基团，R 1是氢原子，取代或未取代的低级烷基或芳基，R 2是氢原子，低级烷基或芳烷基，R 3表示氢原子，有机磺酰基或-C（ = Y）-R4，其中R4为氢原子或有机残基，Y为氧或硫原子，条件是当R3为氢原子时，R1为氢原子以外的基团，R2为氢原子 。 这些酰胺吡唑衍生物或其盐具有优异的p38MAP激酶抑制活性，因此可用于预防或治疗与肿瘤坏死因子α，白细胞介素1，白介素6或环加氧酶II相关的疾病。

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：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。

公开(公告)号：US07799775B2

公开(公告)日：2010-09-21

申请号：US10590707

申请日：2005-02-25

申请人： Michitaka Sato ,  Teruaki Matsui ,  Akira Asagarasu ,  Hiroyuki Hayashi ,  Sei-ichi Araki ,  Satoru Tamaoki ,  Nobuyuki Takahashi ,  Yukinao Yamauchi ,  Yoshiko Yamamoto ,  Norio Yamamoto ,  Chisato Ogawa

发明人： Michitaka Sato ,  Teruaki Matsui ,  Akira Asagarasu ,  Hiroyuki Hayashi ,  Sei-ichi Araki ,  Satoru Tamaoki ,  Nobuyuki Takahashi ,  Yukinao Yamauchi ,  Yoshiko Yamamoto ,  Norio Yamamoto ,  Chisato Ogawa

IPC分类号： A01N43/54 ,  A01N43/90 ,  A01N43/04 ,  A01N43/58 ,  A01N43/60 ,  A61K31/54 ,  A61K31/505 ,  A61K31/519 ,  A61K31/535 ,  A61K31/675 ,  A61K31/50 ,  A61K31/495

CPC分类号： C07D495/14 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5395 ,  A61K45/06 ,  C07D401/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61K2300/00

摘要： This invention provides pyrimidine derivatives represented by a formula, in the formula, ring A stands for carbocyclic group or heterocyclic group, X1 stands for hydrogen, lower alkyl, amino, etc., X2 stands for hydrogen or lower alkyl, Y stands for a direct bond or sulfur or nitrogen, n stands for an integer of 0-4, and Ar stands for a group of the following formula, or a salt thereof, which concurrently exhibit 5-HT1A agonistic activity and 5-HT3 antagonistic activity and are useful for therapy and treatments of diseases such as IBS. The invention furthermore provides a therapeutic method of IBS, characterized by having 5-HT1A agonistic activity and 5-HT3 antagonistic activity work simultaneously and cooperatively in vivo, which comprises either administering 5-HT3 antagonistic agent which concurrently exhibits 5-HT1A agonistic activity, or administering 5-HT1A agonistic agent and 5-HT3 antagonistic agent simultaneously, in sequence or at an interval.

摘要翻译： 本发明提供下式所示的嘧啶衍生物，式中环A代表碳环基或杂环基，X1代表氢，低级烷基，氨基等，X2代表氢或低级烷基，Y代表直链 键或硫或氮，n表示0-4的整数，Ar表示下式的基团或其盐，其同时表现出5-HT1A激动活性和5-HT 3拮抗活性，并且可用于 治疗和治疗IBS等疾病。 本发明还提供了IBS的治疗方法，其特征在于在体内同时和协同地具有5-HT1A激动活性和5-HT3拮抗活性，其包括施用同时显示5-HT1A激动活性的5-HT3拮抗剂，或 同时按照或间隔施用5-HT1A激动剂和5-HT3拮抗剂。

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：US07087624B2

公开(公告)日：2006-08-08

申请号：US10693461

申请日：2003-10-27

申请人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

发明人： Nobuyoshi Minami ,  Michitaka Sato ,  Koichi Hasumi ,  Norio Yamamoto ,  Katsuyuki Keino ,  Teruaki Matsui ,  Arihiro Kanada ,  Shuji Ohta ,  Takahisa Saito ,  Shuichiro Sato ,  Akira Asagarasu ,  Satoshi Doi ,  Motohiro Kobayashi ,  Jun Sato ,  Hajime Asano

IPC分类号： A61K31/44 ,  C07D40/00

CPC分类号： C07D231/12 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/4725 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  Y02A50/411

摘要： Substituted pyrazole compounds represented by formula (I), or salts thereof are disclosed, wherein R1 is —CH(OH)—CH(R4)-(A)n-Y, —CH2—CH(R4)-(A)n-Y, —CO-B1-A-Y or the like (wherein A is a lower alkylene; Y is an aryl group which may be substituted, for example, by halogen, or the like; R4 is a hydrogen atom or a lower alkyl group; B1 is —CH(R4)— or —N(R4)—; and n is 0 or 1); R2 is a hydrogen atom, a lower alkyl group which may be substituted by hydroxyl or the like, or an aralkyl group; R3 is a phenyl group which may be substituted by halogen or the like, or a pyridyl group; and Q is a pyridyl or quinolyl group. These substituted pyrazole compounds or their salts have an excellent p38MAP kinase inhibiting effect and are hence useful in the prevention or treatment of tumor necrosis factor α-related diseases, interleukin 1-related diseases, interleukin 6-related diseases or cyclooxygenase II-related diseases

摘要翻译： 公开了由式（I）表示的取代的吡唑化合物或其盐，其中R 1是-CH（OH）-CH（R 4） - （A） -CH（R 4） - （A）n -Y， - CO（CH 2） -B 1 -I 1等（其中A是低级亚烷基; Y是可以被卤素取代的芳基等）; R 4， SUP>是氢原子或低级烷基; B 1是-CH（R 4） - 或-N（R 4） - ;和n为0或1）; R 2是氢原子，可以被羟基等取代的低级烷基或芳烷基; R 3是可以被卤素等取代的苯基或吡啶基; Q为吡啶基或喹啉基。 这些取代的吡唑化合物或其盐具有优异的p38MAP激酶抑制作用，因此可用于预防或治疗肿瘤坏死因子α相关疾病，白细胞介素1相关疾病，白细胞介素6相关疾病或环氧合酶II相关疾病

公开(公告)号：US09200008B2

公开(公告)日：2015-12-01

申请号：US13701896

申请日：2011-07-01

申请人： Hiroshi Uchida ,  Akira Asagarasu ,  Teruaki Matsui

发明人： Hiroshi Uchida ,  Akira Asagarasu ,  Teruaki Matsui

IPC分类号： C07D471/04 ,  C07D498/04 ,  C07D207/34 ,  C07D231/40 ,  C07D277/20 ,  C07D277/42 ,  C07D307/68 ,  C07D403/12 ,  C07D405/14 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C07D487/04 ,  C07D491/052 ,  C07F5/02

CPC分类号： C07D498/04 ,  C07D207/34 ,  C07D231/40 ,  C07D277/20 ,  C07D277/42 ,  C07D307/68 ,  C07D403/12 ,  C07D405/14 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D491/052 ,  C07F5/025

摘要： A novel heterocyclic compound or a salt thereof useful for selectively inhibiting the degradation of p27Kip1 is provided. The compound or the salt thereof is represented by the following formula (1): wherein A represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, the group A may have a substituent; the ring B represents a 5- to 8-membered monocyclic heterocyclic ring or a condensed ring containing the monocyclic heterocyclic ring, the ring B may have a substituent; the ring C represents an aromatic ring, the ring C may have a substituent; L represents a linker comprising a main chain having 3 to 5 atoms selected from the group consisting of a carbon atom, a nitrogen atom, an oxygen atom and a sulfur atom, wherein at least one atom in the main chain is a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, the linker L may have a substituent; and n is 0 or 1.

摘要翻译： 提供了可用于选择性抑制p27Kip1降解的新型杂环化合物或其盐。 化合物或其盐由下式（1）表示：其中A表示烷基，环烷基，芳基或杂环基，基团A可以具有取代基; 环B表示5至8元单环杂环或含有单环杂环的稠环，环B可以具有取代基; 环C表示芳香环，环C可以具有取代基; L表示包含选自碳原子，氮原子，氧原子和硫原子的3至5个原子的主链的连接体，其中主链中的至少一个原子是选自以下的杂原子 由氮原子，氧原子和硫原子组成的基团，连接体L可以具有取代基; n为0或1。