公开(公告)号：EP2739621B1

公开(公告)日：2017-06-21

申请号：EP12759833.2

申请日：2012-08-01

申请人： Astellas Pharma Inc.

发明人： SUGASAWA, Keizo ,  MIYAFUJI, Akio ,  SUZUKI, Kenichi ,  AWAMURA, Yuji

IPC分类号： C07D417/14 ,  A61K31/496 ,  A61P7/04

CPC分类号： C07D417/14

公开(公告)号：EP2860175A1

公开(公告)日：2015-04-15

申请号：EP13804693.3

申请日：2013-06-11

申请人： Astellas Pharma Inc.

发明人： KAWAZOE, Souichirou ,  AKIBA, Takahiro ,  SATO, Kiichi ,  MIYAFUJI, Akio ,  OBITSU, Kazuyoshi ,  ITOH, Junji ,  HIRASAWA, Shun ,  KOSHIO, Hiroyuki

IPC分类号： C07D223/16 ,  C07C311/19

CPC分类号： C07D223/16 ,  C07C51/09 ,  C07C51/367 ,  C07C67/31 ,  C07C303/40 ,  C07C311/21 ,  C07D301/00

摘要： The present invention provides a method for producing a 4,4,7-trifluoro-1,2,3,4-tetrahydro-5H-1-benzazepine compound which has an superior agonistic activity to an arginine vasopressin V2 receptor and is useful as an active ingredient for a pharmaceutical composition for preventing and/or treating urinary frequency, urinary incontinence, enuresis, central diabetes insipidus, nocturia, nocturnal enuresis, or the like; and useful intermediates for use in the methods. The production method of the present invention is suitable for the industrial production of a medicament, because of a smaller number of steps, a higher yield, and a lower cost, as compared with the methods in the related art.

摘要翻译： 本发明提供了一种方法用于产生在精氨酸加压素V2受体具有优越的激动活性并是作为在一个有用4,4,7三氟-1,2,3,4-四氢-5H-1-苯并吖庚因化合物 用于预防和/或治疗尿频，尿失禁，遗尿症，中枢性尿崩症，夜尿频，夜间遗尿症等的药物组合物活性成分; 和有用的中间体，用于在方法中使用。 本发明的制造方法适合于工业生产的药物，因为更小的数量的步骤，更高的产量和更低的成本，因为与现有技术中的方法相比。

公开(公告)号：EP3246325B1

公开(公告)日：2020-03-25

申请号：EP17176670.2

申请日：2012-08-01

申请人： Astellas Pharma Inc.

发明人： SUGASAWA, Keizo ,  MIYAFUJI, Akio ,  SUZUKI, Kenichi ,  AWAMURA, Yuji

IPC分类号： C07D417/14 ,  A61K31/496 ,  A61P7/04

公开(公告)号：EP3246325A1

公开(公告)日：2017-11-22

申请号：EP17176670.2

申请日：2012-08-01

申请人： Astellas Pharma Inc.

发明人： SUGASAWA, Keizo ,  MIYAFUJI, Akio ,  SUZUKI, Kenichi ,  AWAMURA, Yuji

IPC分类号： C07D417/14 ,  A61K31/496 ,  A61P7/04

摘要： The purpose of the present invention is to provide crystals of 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexyl piperazin-1-yl) thiazol-2-yl] carbamoyl} pyridin-2-yl) piperidine-4-carboxylic acid maleic acid salt that can ensure constant quality and constant effects as a drug substance for medicines, and that can be stably supplied in mass production such as industrial production. The present invention relates to crystals of 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexyl piperazin-1-yl) thiazol-2-yl] carbamoyl} pyridin-2-yl) piperidine-4-carboxylic acid maleic acid salt with endothermic peak top temperatures in differential scanning calorimeter analysis of between approximately 229 and 232 degree C, and between approximately 300 and 303 degree C. The crystals of the present invention are with excellent oral absorption, can be stably supplied in mass production such as industrial production or the like, and can be used as an active ingredient in a pharmaceutical composition for preventing and/or treating various types of thrombocytopenia.

摘要翻译： 本发明的目的是提供1-（3-氯-5 - {[4-（4-氯噻吩-2-基）-5-（4-环己基哌嗪-1-基）噻唑-2-基] 嘧啶-4-基]氨基甲酰基}吡啶-2-基）哌啶-4-羧酸马来酸盐，其可以确保作为药物原料的恒定质量和恒定效果，并且可以在工业生产等大规模生产中稳定地供应。 本发明涉及1-（3-氯-5 - {[4-（4-氯噻吩-2-基）-5-（4-环己基哌嗪-1-基）噻唑-2-基]氨基甲酰基} 吡啶-2-基）哌啶-4-羧酸马来酸盐在差示扫描量热计分析中具有介于约229和232℃之间以及介于约300和303℃之间的吸热峰顶温度。本发明的晶体是 具有优异的口服吸收性，可以在工业生产等大量生产中稳定地供应，并且可以用作用于预防和/或治疗各种类型的血小板减少症的药物组合物中的活性成分。

公开(公告)号：EP2739621A1

公开(公告)日：2014-06-11

申请号：EP12759833.2

申请日：2012-08-01

申请人： Astellas Pharma Inc.

发明人： SUGASAWA, Keizo ,  MIYAFUJI, Akio ,  SUZUKI, Kenichi ,  AWAMURA, Yuji

IPC分类号： C07D417/14 ,  A61K31/496 ,  A61P7/04

CPC分类号： C07D417/14

摘要： The purpose of the present invention is to provide crystals of 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexyl piperazin-1-yl) thiazol-2-yl] carbamoyl} pyridin-2-yl) piperidine-4-carboxylic acid maleic acid salt that can ensure constant quality and constant effects as a drug substance for medicines, and that can be stably supplied in mass production such as industrial production. The present invention relates to crystals of 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexyl piperazin-1-yl) thiazol-2-yl] carbamoyl} pyridin-2-yl) piperidine-4-carboxylic acid maleic acid salt with endothermic peak top temperatures in differential scanning calorimeter analysis of between approximately 229 and 232 degree C, and between approximately 300 and 303 degree C. The crystals of the present invention are with excellent oral absorption, can be stably supplied in mass production such as industrial production or the like, and can be used as an active ingredient in a pharmaceutical composition for preventing and/or treating various types of thrombocytopenia.