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1. 发明授权

US08530456B2 Sonic hedgehog modulators 有权
标题翻译：声波刺猬调制器
公开(公告)号：US08530456B2
公开(公告)日：2013-09-10
申请号：US12988755
申请日：2009-04-21
申请人： Lee F. Peng , Julia Lamenzo , Nicole Maloof , Kazuo Nakai , Benjamin Stanton , Sara Jean Buhrlage , Lawrence MacPherson , Michel Weiwer , Stuart L. Schreiber
发明人： Lee F. Peng , Julia Lamenzo , Nicole Maloof , Kazuo Nakai , Benjamin Stanton , Sara Jean Buhrlage , Lawrence MacPherson , Michel Weiwer , Stuart L. Schreiber
IPC分类号： C07D495/06 , C07D493/06 , C07D495/16 , C07D493/16 , A61K31/395 , A61P35/00
CPC分类号： C07D267/00 , C07D269/02 , C07D413/12
摘要： The present invention relates to macrocyclic small molecule inhibitors of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. Such small molecule modulators of the Sonic Hedgehog signaling pathway are useful in the treatment of proliferative diseases (e.g., basal cell carcinoma, Gorlin syndrome, medulloblastoma, or pancreatic cancer), pulmonary diseases (e.g., interstitial pnuemonitis or interstitial pulmonary fibrosis), and developmental disorders (e.g., phocomelia or cyclopia). Novel non-natural macrocycles are provided that inhibit Sonic Hedgehog induced-protein transcription.
摘要翻译：本发明涉及Sonic Hedgehog信号通路的大环小分子抑制剂，其合成及其中间体。 Sonic Hedgehog信号通路的这种小分子调节剂可用于治疗增殖性疾病（例如基底细胞癌，Gorlin综合征，成神经管细胞瘤或胰腺癌），肺部疾病（例如间质性血管炎或间质性肺纤维化）和发育性疾病（例如，青光眼或环状）。提供新的非天然大环以抑制声刺猬诱导蛋白转录。

2. 发明申请

US20110172233A1 SONIC HEDGEHOG MODULATORS 有权
标题翻译： SONIC HEDGEHOG调制器
公开(公告)号：US20110172233A1
公开(公告)日：2011-07-14
申请号：US12988755
申请日：2009-04-21
申请人： Lee F. Peng , Julia Lamenzo , Nicole Maloof , Kazuo Nakai , Benjamin Stanton , Sara Jean , Lawrence Macpherson , Michel Weiwer , Stuart L. Schreiber
发明人： Lee F. Peng , Julia Lamenzo , Nicole Maloof , Kazuo Nakai , Benjamin Stanton , Sara Jean , Lawrence Macpherson , Michel Weiwer , Stuart L. Schreiber
IPC分类号： A61K31/5377 , C07D267/00 , C07D413/12 , A61K31/395 , A61K31/4427 , A61K31/4523 , C12N5/07 , A61P35/00
CPC分类号： C07D267/00 , C07D269/02 , C07D413/12
摘要： The present invention relates to relates to macrocyclic small molecule inhibitors of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. Such small molecule modulators of the Sonic Hedgehog signaling pathway are useful in the treatment of proliferative diseases (e.g., basal cell carcinoma, Gorlin syndrome, medulloblastoma, or pancreatic cancer), pulmonary diseases (e.g., interstitial pnuemonitis or interstitial pulmonary fibrosis), and developmental disorders (e.g., phocomelia or cyclopia). Novel non-natural macrocycles are provided that inhibit Sonic Hedgehog induced-protein transcription.
摘要翻译：本发明涉及Sonic Hedgehog信号通路的大环小分子抑制剂，其合成及其中间体。 Sonic Hedgehog信号通路的这种小分子调节剂可用于治疗增殖性疾病（例如基底细胞癌，Gorlin综合征，成神经管细胞瘤或胰腺癌），肺部疾病（例如间质性血管炎或间质性肺纤维化）和发育性疾病（例如，青光眼或环状）。提供新的非天然大环以抑制声刺猬诱导蛋白转录。

3. 发明申请

US20120309234A1 CONNECTOR 有权
标题翻译：连接器
公开(公告)号：US20120309234A1
公开(公告)日：2012-12-06
申请号：US13485099
申请日：2012-05-31
申请人： Mitsunori Kitajima , Youjirou Hashimoto , Kazuo Nakai
发明人： Mitsunori Kitajima , Youjirou Hashimoto , Kazuo Nakai
IPC分类号： H01R24/00
CPC分类号： H01R13/5202 , H01R13/506
摘要： A connector includes a one-piece rubber plug (30) arranged to cover a rear surface (10R) of an inner housing (10) and has seal holes (31) aligned with cavities 12. An outer housing (20) has a tubular portion (21) surrounding the inner housing (10) and a rear wall (24) covering a rear surface (30R) of the one-piece rubber plug (30). The rear wall (24) has insertion holes (25) aligned with the seal holes (31). Locking holes (26A, 26B) are open on a rear surface (24R) of the rear wall (24), and locks (17A, 17B) on the inner housing (10) engage with the locking holes (26A, 26B) to lock the housings (10, 20) in an assembled state.
摘要翻译：连接器包括一体式橡胶塞（30），其布置成覆盖内壳体（10）的后表面（10R）并且具有与空腔12对准的密封孔（31）。外壳体（20）具有管状部分（21）和覆盖所述一体式橡胶塞（30）的后表面（30R）的后壁（24）。后壁（24）具有与密封孔（31）对准的插入孔（25）。锁定孔（26A，26B）在后壁（24）的后表面（24R）上打开，并且内壳体（10）上的锁定件（17A，17B）与锁定孔（26A，26B）接合以锁定壳体（10,20）处于组装状态。

4. 发明申请

US20110039822A1 HETEROCYCLIC JANUS KINASE 3 INHIBITORS 审中-公开
标题翻译：杂交种JANUS KINASE 3抑制剂
公开(公告)号：US20110039822A1
公开(公告)日：2011-02-17
申请号：US12914475
申请日：2010-10-28
申请人： Takayuki INOUE , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
发明人： Takayuki INOUE , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
IPC分类号： A61K31/437 , C07D471/04 , C07D471/14 , A61K31/496 , A61K31/506 , A61K31/5377 , A61K31/541 , A61P17/06 , A61P19/02 , A61P37/00 , A61P37/06
CPC分类号： C07D451/04 , C07D471/04 , C07D471/14 , C07D519/00
摘要： The present invention provides a compound having an excellent JAK3 inhibition activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases, inflammatory diseases, and allergic diseases.As a result of studies on a novel condensed heterocyclic derivative, the inventors have found that a compound having a cross-linked structure has an excellent JAK3 inhibition activity, and have completed the present invention.In other words, it is verified that the compound according to the present invention has an inhibition activity against JAK3 and is thus useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission (e.g., rejection during organ/tissue transplantation, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, atopic dermatitis, Alzheimer's disease, and atherosclerotic disease), or diseases caused by abnormal cytokine signal transmission (e.g., cancer and leukemia).
摘要翻译：本发明提供具有优异的JAK3抑制活性的化合物，可用作治疗和/或预防各种免疫疾病，包括自身免疫性疾病，炎症性疾病和过敏性疾病的药剂的活性成分。作为研究新型稠合杂环衍生物的结果，本发明人发现具有交联结构的化合物具有优异的JAK3抑制活性，并且完成了本发明。换句话说，证实了本发明的化合物对JAK3具有抑制活性，因此可用作治疗或预防由不期望的细胞因子信号传导引起的疾病的药剂的活性成分（例如器官/ 组织移植，自身免疫性疾病，多发性硬化，类风湿性关节炎，牛皮癣，哮喘，特应性皮炎，阿尔茨海默病和动脉粥样硬化疾病）或由异常细胞因子信号传导引起的疾病（例如癌症和白血病）。

5. 发明授权

US07166598B2 Piperazine derivatives 失效
标题翻译：哌嗪衍生物
公开(公告)号：US07166598B2
公开(公告)日：2007-01-23
申请号：US10968473
申请日：2004-10-20
申请人： Kazuhiko Take , Nobukiyo Konishi , Shinji Shigenaga , Natsuko Kayakiri , Hidenori Azami , Yoshiteru Eikyu , Kazuo Nakai , Junya Ishida , Masataka Morita
发明人： Kazuhiko Take , Nobukiyo Konishi , Shinji Shigenaga , Natsuko Kayakiri , Hidenori Azami , Yoshiteru Eikyu , Kazuo Nakai , Junya Ishida , Masataka Morita
IPC分类号： A61K31/5355 , C07D413/06 , A61K31/496 , C07D401/06
CPC分类号： C07D401/06 , C07D241/04 , C07D401/14 , C07D403/06 , C07D403/14 , C07D413/06 , C07D413/14 , C07D417/06 , C07D471/04 , C07D491/08 , C07D495/04 , C07D498/04 , C07D498/08 , C07F7/1804
摘要： This invention relates to piperazine derivatives of the formula: wherein each symbol is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human being or animals.
摘要翻译：本发明涉及下式的哌嗪衍生物：其中每个符号如说明书中所定义，及其药学上可接受的盐，其制备方法，包含其的药物组合物及其用于治疗或预防的用途速激肽介导的人类或动物疾病。

6. 发明申请

US20090270376A1 HETEROCYCLIC JANUS KINASE 3 INHIBITORS 有权
标题翻译：杂交种JANUS KINASE 3抑制剂
公开(公告)号：US20090270376A1
公开(公告)日：2009-10-29
申请号：US12065234
申请日：2006-12-25
申请人： Takayuki Inoue , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
发明人： Takayuki Inoue , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
IPC分类号： A61K31/437 , C07D471/04 , C07D471/14 , A61K31/496 , A61K31/5377 , A61K31/541 , A61P37/00 , A61P25/28 , A61P35/00
CPC分类号： C07D451/04 , C07D471/04 , C07D471/14 , C07D519/00
摘要： The present invention provides a compound of formula (I) having an excellent JAK3 inhibition activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases inflammatory diseases, and allergic diseases. The compound according to the present invention has an inhibition activity against JAK3 and is thus useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission (e.g., rejection during organ/tissue transplantation, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, atopic dermatitis, Alzheimer's disease, and atherosclerotic disease), or diseases caused by abnormal cytokine signal transmission (e.g., cancer and leukemia).
摘要翻译：本发明提供了具有优异的JAK3抑制活性的式（I）化合物，并且可用作治疗和/或预防各种免疫疾病，包括自身免疫性疾病炎性疾病和过敏性疾病的药剂的活性成分。根据本发明的化合物对JAK3具有抑制活性，因此可用作治疗或预防由不良细胞因子信号传导引起的疾病（例如器官/组织移植期间的排斥，自身免疫性疾病，多发性硬化症）的活性成分，类风湿性关节炎，牛皮癣，哮喘，特应性皮炎，阿尔茨海默病和动脉粥样硬化疾病）或由异常细胞因子信号传导引起的疾病（例如癌症和白血病）。

7. 发明授权

US07879844B2 Heterocyclic janus kinase 3 inhibitors 有权
标题翻译：杂环janus激酶3抑制剂
公开(公告)号：US07879844B2
公开(公告)日：2011-02-01
申请号：US12065234
申请日：2006-12-25
申请人： Takayuki Inoue , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
发明人： Takayuki Inoue , Akira Tanaka , Kazuo Nakai , Hiroshi Sasaki , Fumie Takahashi , Shohei Shirakami , Keiko Hatanaka , Yutaka Nakajima , Koichiro Mukoyoshi , Hisao Hamaguchi , Shigeki Kunikawa , Yasuyuki Higashi
IPC分类号： A61K31/437 , A61K31/496 , A61K31/5377 , A61K31/541 , C07D471/04 , C07D471/14 , A61P37/00 , A61P25/28 , A61P35/00
CPC分类号： C07D451/04 , C07D471/04 , C07D471/14 , C07D519/00
摘要： The present invention provides a compound of formula (I) having an excellent JAK3 inhibition activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases inflammatory diseases, and allergic diseases. The compound according to the present invention has an inhibition activity against JAK3 and is thus useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission (e.g., rejection during organ/tissue transplantation, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, atopic dermatitis, Alzheimer's disease, and atherosclerotic disease), or diseases caused by abnormal cytokine signal transmission (e.g., cancer and leukemia).
摘要翻译：本发明提供了具有优异的JAK3抑制活性的式（I）化合物，并且可用作治疗和/或预防各种免疫疾病，包括自身免疫性疾病炎性疾病和过敏性疾病的药剂的活性成分。根据本发明的化合物对JAK3具有抑制活性，因此可用作治疗或预防由不良细胞因子信号传导引起的疾病（例如器官/组织移植期间的排斥，自身免疫性疾病，多发性硬化症）的活性成分，类风湿性关节炎，牛皮癣，哮喘，特应性皮炎，阿尔茨海默病和动脉粥样硬化疾病）或由异常细胞因子信号传导引起的疾病（例如癌症和白血病）。

8. 发明申请

US20100216798A1 FUSED HETEROCYCLES AS LCK INHIBITORS 审中-公开
标题翻译：熔融杂环化合物作为LCK抑制剂
公开(公告)号：US20100216798A1
公开(公告)日：2010-08-26
申请号：US11993229
申请日：2006-07-27
申请人： Kazuo Nakai , Fumie Takahashi , Kazuya Fujita , Yoshihiro Kozuki , Koichiro Mukoyoshi , Masamichi Inami , Norio Asai
发明人： Kazuo Nakai , Fumie Takahashi , Kazuya Fujita , Yoshihiro Kozuki , Koichiro Mukoyoshi , Masamichi Inami , Norio Asai
IPC分类号： A61K31/5025 , C07D487/04 , A61K31/519 , A61P37/00 , A61P11/06 , A61P37/06
CPC分类号： C07D487/04
摘要： There is provided fused heterocycles of imidazopyridazine or pyrazolopyrimidine derivative represented by the formula (I), which have excellent Lck inhibitory activity and are useful for a medicament particularly an immunosuppressive agent. [wherein one of Y and Z is C atom, and the other is N atom; —X— is —N(R1)— or the like, —R1 represents hydrogen or the like, -A- represents bond or the like, —R2 is cycloalkyl, aryl or the like, -E- is bond or the like, —R3 is aryl, aromatic heterocycle or the like, —R4, —R5 and —R6 are the same or different, each being hydrogen or the like.]
摘要翻译：提供由式（I）表示的咪唑并哒嗪或吡唑并嘧啶衍生物的稠合杂环，其具有优异的Lck抑制活性，并且可用于药物，特别是免疫抑制剂。 [其中Y和Z之一是C原子，另一个是N原子; -X-是-N（R 1） - 等，-R 1表示氢等，-A-表示键等，-R 2是环烷基，芳基等，-E-是键等， -R3是芳基，芳香族杂环等，-R4，-R5和-R6相同或不同，各自为氢等。

9. 发明申请

US20070123532A1 PIPERAZINE DERIVATIVES 审中-公开
标题翻译：哌嗪衍生物
公开(公告)号：US20070123532A1
公开(公告)日：2007-05-31
申请号：US11562149
申请日：2006-11-21
申请人： Kazuhiko Take , Nobukiyo Konishi , Shinji Shigenaga , Natsuko Kayakiri , Hidenori Azami , Yoshiteru Eikyu , Kazuo Nakai , Junya Ishida , Masataka Morita
发明人： Kazuhiko Take , Nobukiyo Konishi , Shinji Shigenaga , Natsuko Kayakiri , Hidenori Azami , Yoshiteru Eikyu , Kazuo Nakai , Junya Ishida , Masataka Morita
IPC分类号： A61K31/5377 , A61K31/496
CPC分类号： C07D401/06 , C07D241/04 , C07D401/14 , C07D403/06 , C07D403/14 , C07D413/06 , C07D413/14 , C07D417/06 , C07D471/04 , C07D491/08 , C07D495/04 , C07D498/04 , C07D498/08 , C07F7/1804
摘要： This invention relates to piperazine derivatives of the formula: wherein each symbol is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human being or animals.
摘要翻译：本发明涉及下式的哌嗪衍生物：其中每个符号如说明书中所定义，及其药学上可接受的盐，其制备方法，包含其的药物组合物及其用于治疗或预防的用途速激肽介导的人类或动物疾病。

10. 发明授权

US5327399A Multivibrator waveform monitoring system 失效
标题翻译：多谐振荡器波形监测系统
公开(公告)号：US5327399A
公开(公告)日：1994-07-05
申请号：US795191
申请日：1991-11-19
申请人： Masaaki Asada , Kazuo Nakai
发明人： Masaaki Asada , Kazuo Nakai
IPC分类号： G01V1/155 , B06B1/18 , G01V1/04 , G01V1/135 , G01V1/28 , H04R23/00
CPC分类号： B06B1/18 , G01V1/135 , H04R23/00
摘要： A multivibrator waveform monitoring system uses a plurality of seismic energy sources for giving vibrations to strata and a prospector, connected to a geophone, for measuring reflected vibrations. Each of the plurality of seismic energy sources includes a vibrator, a communication unit and a control unit for controlling the starting of the vibrator based on phase difference cancellation information and an operation starting instruction from the prospector. The prospector includes a communication unit and a synchronization control unit for controlling the synchronization of each of the seismic energy sources. The synchronization control unit receives detected information relating to the vibrations of the vibrator by the communication unit, compares a phase difference of vibrations between a master unit which is one of the seismic energy sources and each of slave units which are the rest of the seismic energy sources, calculates phase difference cancellation information for cancelling each phase difference, and transmits the phase difference cancellation information and an operation starting instruction for starting the vibrator by the communication unit. A timing for starting the vibrators of the vibrator for each seismic energy source is adjusted based on the phase difference cancellation information, to thereby make the phase of vibrations of the vibrator of each of the slave seismic energy sources to be the same as the phase of vibrations of the master unit.
摘要翻译：多谐振荡器波形监测系统使用多个地震能量来向地层提供振动，并且连接到地震检波器的探测器用于测量反射的振动。多个地震能量源中的每一个包括振动器，通信单元和控制单元，用于基于相位差消除信息和来自探测器的操作开始指令来控制振动器的启动。探测器包括通信单元和用于控制每个地震能量源的同步的同步控制单元。同步控制单元通过通信单元接收与振动器的振动相关的检测信息，比较作为地震能源之一的主单元和作为其余地震能量的各个从单元之间的振动的相位差源，计算用于消除每个相位差的相位差消除信息，并且通过通信单元发送相位差消除信息和用于启动振动器的操作开始指令。基于相位差消除信息来调整用于启动每个地震能量源的振动器的振动器的定时，从而使得每个从地震能量源的振动器的振动相位与主机振动。

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