公开(公告)号：US08765945B2

公开(公告)日：2014-07-01

申请号：US13023140

申请日：2011-02-08

申请人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

发明人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

IPC分类号： C07D237/36

CPC分类号： C07D405/06 ,  C07D249/08 ,  C07D401/04 ,  C07D403/06 ,  C07D471/06

摘要： Provided herein are processes for synthesizing dihydropyridophthalazinone derivatives, such as for example, 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and its stereoisomers, which are potent poly(ADP-ribose)polymerase (PARP) inhibitors as well as novel synthetic intermediate compounds.

摘要翻译： 本文提供了合成二氢吡啶并二氮杂萘酮衍生物的方法，例如5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基） 9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮及其立体异构体，它们是有效的聚（ADP-核糖）聚合酶（PARP）抑制剂以及新的合成中间体化合物。

公开(公告)号：US08735392B2

公开(公告)日：2014-05-27

申请号：US13277607

申请日：2011-10-20

申请人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Shichun Peng

发明人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Shichun Peng

IPC分类号： A01N43/58 ,  A61K31/495

CPC分类号： C07D471/06

摘要： Provided herein are (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, and methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.

摘要翻译： 本文提供的是（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H- - 吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲磺酸盐形式，包括晶型，及其制备方法。 包含（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢 - 还提供了使用（8S，9R）-5-氟-8-（4-氟苯基）-9（7H） - 酮的方法，使用2-吡啶并[4,3,2- - （1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲苯磺酸盐 治疗疾病或病症，如癌症。

公开(公告)号：US08724765B2

公开(公告)日：2014-05-13

申请号：US13502477

申请日：2010-10-22

申请人： Yongbo Liu ,  Hongwei Zhang ,  Jian Li ,  Zhaoli Zhang ,  Liang Fan ,  Zhen Liu ,  Yutao Jia

发明人： Yongbo Liu ,  Hongwei Zhang ,  Jian Li ,  Zhaoli Zhang ,  Liang Fan ,  Zhen Liu ,  Yutao Jia

IPC分类号： H03D3/24

CPC分类号： H03L7/10 ,  H03L7/085 ,  H03L7/093

摘要： The present invention provides a locking method and system, and the method includes: a locking system performing a phase discrimination and conversion process to an input signal Fi of an external standard source and a feedback output signal F0 of a local thermostatic crystal oscillator which pass through a frequency division, to generate a clock signal clk and a signal sign which is used to denote a frequency size relationship between the signal Fi and the signal F0, and performing a filtering process to the signal clk and the signal sign, and performing a voltage controlled oscillation process to a signal ahead used to denote that the frequency of the signal F0 is lower than the frequency of the signal Fi and a signal lag used to denote that the frequency of the signal F0 is higher than the frequency of the signal Fi, to implement a locking of the signal F0 and the signal Fi.

摘要翻译： 本发明提供一种锁定方法和系统，并且该方法包括：对外部标准源的输入信号Fi和通过的本地恒温晶体振荡器的反馈输出信号F0执行相位鉴别和转换处理的锁定系统 分频，产生时钟信号clk和用于表示信号Fi和信号F0之间的频率大小关系的信号，并对信号clk和信号进行滤波处理，并执行电压 控制振荡处理到前面的信号，用于表示信号F0的频率低于信号Fi的频率，以及用于表示信号F0的频率高于信号Fi的频率的信号滞后， 以实现信号F0和信号Fi的锁定。

公开(公告)号：US20120213268A1

公开(公告)日：2012-08-23

申请号：US13502477

申请日：2010-10-22

申请人： Yongbo Liu ,  Hongwei Zhang ,  Jian Li ,  Zhaoli Zhang ,  Liang Fan ,  Zhen Liu ,  Yutao Jia

发明人： Yongbo Liu ,  Hongwei Zhang ,  Jian Li ,  Zhaoli Zhang ,  Liang Fan ,  Zhen Liu ,  Yutao Jia

IPC分类号： H03L7/08 ,  H03B19/00 ,  H03K7/08

CPC分类号： H03L7/10 ,  H03L7/085 ,  H03L7/093

摘要： The present invention provides a locking method and system, and the method includes: a locking system performing a phase discrimination and conversion process to an input signal Fi of an external standard source and a feedback output signal F0 of a local thermostatic crystal oscillator which pass through a frequency division, to generate a clock signal clk and a signal sign which is used to denote a frequency size relationship between the signal Fi and the signal F0, and performing a filtering process to the signal clk and the signal sign, and performing a voltage controlled oscillation process to a signal ahead used to denote that the frequency of the signal F0 is lower than the frequency of the signal Fi and a signal lag used to denote that the frequency of the signal F0 is higher than the frequency of the signal Fi, to implement a locking of the signal F0 and the signal Fi.

摘要翻译： 本发明提供一种锁定方法和系统，并且该方法包括：对外部标准源的输入信号Fi和通过的本地恒温晶体振荡器的反馈输出信号F0执行相位鉴别和转换处理的锁定系统 分频，产生时钟信号clk和用于表示信号Fi和信号F0之间的频率大小关系的信号，并对信号clk和信号进行滤波处理，并执行电压 控制振荡处理到前面用于表示信号F0的频率低于信号Fi的频率的信号，以及用于表示信号F0的频率高于信号Fi的频率的信号滞后， 以实现信号F0和信号Fi的锁定。

公开(公告)号：US20120129865A1

公开(公告)日：2012-05-24

申请号：US13277607

申请日：2011-10-20

申请人： BING WANG ,  DANIEL CHU ,  Yongbo Liu ,  Shichun Peng

发明人： BING WANG ,  DANIEL CHU ,  Yongbo Liu ,  Shichun Peng

IPC分类号： A61K31/5025 ,  A61P35/00 ,  A61P35/02 ,  C07D487/04

CPC分类号： C07D471/06

摘要： Provided herein are (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, and methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.

摘要翻译： 本文提供的是（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H- - 吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲磺酸盐形式，包括晶型，及其制备方法。 包含（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢 - 还提供了使用（8S，9R）-5-氟-8-（4-氟苯基）-9（7H） - 酮的方法，使用2-吡啶并[4,3,2- - （1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲苯磺酸盐 治疗疾病或病症，如癌症。

公开(公告)号：US20110196153A1

公开(公告)日：2011-08-11

申请号：US13023140

申请日：2011-02-08

申请人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

发明人： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

IPC分类号： C07D471/04 ,  C07D405/06 ,  C07D249/08 ,  C07D403/06 ,  C07D401/04

CPC分类号： C07D405/06 ,  C07D249/08 ,  C07D401/04 ,  C07D403/06 ,  C07D471/06

摘要： Provided herein are processes for synthesizing dihydropyridophthalazinone derivatives, such as for example, 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and its stereoisomers, which are potent poly(ADP-ribose)polymerase (PARP) inhibitors as well as novel synthetic intermediate compounds.

摘要翻译： 本文提供了合成二氢吡啶并二氮杂萘酮衍生物的方法，例如5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基） 9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮及其立体异构体，其是有效的聚（ADP-核糖）聚合酶（PARP）抑制剂以及新的合成中间体化合物。