公开(公告)号：US20080287680A1

公开(公告)日：2008-11-20

申请号：US10588857

申请日：2005-02-07

申请人： Yusuke Ishii ,  Kouji Takaoka ,  Masatoshi Inakoshi ,  Shuichi Nakagawa ,  Koji Nagata ,  Naoki Yorimoto ,  Makoto Takeuchi ,  Yasuhiro Yonetoku

发明人： Yusuke Ishii ,  Kouji Takaoka ,  Masatoshi Inakoshi ,  Shuichi Nakagawa ,  Koji Nagata ,  Naoki Yorimoto ,  Makoto Takeuchi ,  Yasuhiro Yonetoku

IPC分类号： C07D453/02

CPC分类号： C07D453/02

摘要： A solifenacin succinate-containing composition with less impurities which can be used as a bulk for pharmaceutical is provided.The solifenacin succinate-containing composition of the present invention has a reduced content of especially its optical isomers in comparison with the known compositions containing an acid addition salt of solifenacin, so that it can be used for production of a therapeutic agent containing solifenacin succinate. In addition, the above-described solifenacin succinate-containing composition can be easily produced in accordance with the production method of the present invention.

摘要翻译： 提供了可用作药物的体积较少的杂质的具有较少杂质的索非那新琥珀酸盐组合物。 与含有solifenacin的酸加成盐的已知组合物相比，本发明的索非那新琥珀酸盐组合物特别是其光学异构体的含量降低，因此可用于制备含有索非那新的琥珀酸solifenacin的治疗剂。 此外，根据本发明的制造方法，可以容易地制造上述的solifenacin succinate组合物。

公开(公告)号：US07829715B2

公开(公告)日：2010-11-09

申请号：US11587826

申请日：2005-04-25

申请人： Masatoshi Inakoshi ,  Yusuke Ishii

发明人： Masatoshi Inakoshi ,  Yusuke Ishii

IPC分类号： C07D453/02

CPC分类号： C07D453/02 ,  A61K31/4725 ,  C07D217/06

摘要： There is provided a novel method for producing solifenacin or a salt thereof which is useful as a medicine, particularly a therapeutic agent and/or a preventive agent for a urinary organ system disease such as pollakiuria or urinary incontinence. Illustratively, there are provided (1) a method for producing solifenacin in which 2-(1H-Imidazolylcarbony1)-1-phenyltetrahydroisoquinoline is used as the starting material, (2) a method for producing solifenacin succinate in which (1RS)-phenyltetrahydroisoquinoline-carboxylic acid quinuclidinyl ester is used as the starting material, (3) a method for producing solifenacin in which a lower alkyl quinuclidinyl carbonate is used as the starting material and (4) a method for producing solifenacin in which phenyltetrahydroisoquinoline-carboxylic acid secondary lower alkyl or tertiary lower alkyl ester is used as the starting material and allowed to react with an alkali metal lower alkoxide.

摘要翻译： 提供了一种可用作药物，特别是用于尿液器官系统疾病如尿频或尿失禁的治疗剂和/或预防剂的索利那芬或其盐的新方法。 提供（1）使用2-（1H-咪唑基羰基）-1-苯基四氢异喹啉作为起始原料的索非那新的制造方法，（2）琥珀酸索非那新的制造方法，其中（1RS） - 苯基四氢异喹啉 - 羧酸奎宁环酯用作原料，（3）制备其中使用低级烷基奎宁环基碳酸酯作为起始原料的索非那新的方法，（4）制备索非那新的方法，其中苯基四氢异喹啉羧酸二级低级烷基 或叔低级烷基酯作为原料，并与碱金属低级醇盐反应。

公开(公告)号：US20070185329A1

公开(公告)日：2007-08-09

申请号：US11587826

申请日：2005-04-25

申请人： Masatoshi Inakoshi ,  Yusuke Ishii

发明人： Masatoshi Inakoshi ,  Yusuke Ishii

IPC分类号： C07D453/02

CPC分类号： C07D453/02 ,  A61K31/4725 ,  C07D217/06

摘要： There is provided a novel method for producing solifenacin or a salt thereof which is useful as a medicine, particularly a therapeutic agent and/or a preventive agent for a urinary organ system disease such as pollakiuria or urinary incontinence. Illustratively, there are provided (1) a method for producing solifenacin in which 2-(1H-imidazolylcarbonyl)-1-phenyltetrahydroisoquinoline is used as the starting material, (2) a method for producing solifenacin succinate in which (1RS)-phenyltetrahydroisoquinoline-carboxylic acid quinuclidinyl ester is used as the starting material, (3) a method for producing solifenacin in which a lower alkyl quinuclidinyl carbonate is used as the starting material and (4) a method for producing solifenacin in which phenyltetrahydroisoquinoline-carboxylic acid secondary lower alkyl or tertiary lower alkyl ester is used as the starting material and allowed to react with an alkali metal lower alkoxide.

摘要翻译： 提供了一种可用作药物，特别是用于尿液器官系统疾病如尿频或尿失禁的治疗剂和/或预防剂的索利那芬或其盐的新方法。 （1）制备其中使用2-（1H-咪唑基羰基）-1-苯基四氢异喹啉作为起始原料的索非那新的方法，（2）一种制备其中（1RS） - 苯基四氢异喹啉-2-酮的苯达辛酸solifenacin的方法， 羧酸奎宁环酯用作原料，（3）制备其中使用低级烷基奎宁环基碳酸酯作为起始原料的索非那新的方法，（4）制备索非那新的方法，其中苯基四氢异喹啉羧酸二级低级烷基 或叔低级烷基酯作为原料，并与碱金属低级醇盐反应。

公开(公告)号：US20070191425A1

公开(公告)日：2007-08-16

申请号：US10593079

申请日：2005-03-11

申请人： Masatoshi Inakoshi ,  Yusuke Ishii

发明人： Masatoshi Inakoshi ,  Yusuke Ishii

IPC分类号： A61K31/4709

CPC分类号： A61K31/4709

摘要： To provide a novel method for producing a composition comprising solifenacin or a salt thereof, and a composition comprising solifenacin or a salt thereof as produced by the method, wherein an optionally substituted lower alkyl is added to the 2-position of the quinuclidine of solifenacin. The composition of the present invention contains a highly pure solifenacin, while the unexpected compounds specific to the method in an extremely low content, so that it has very preferable properties as a bulk for pharmaceutical products.

摘要翻译： 提供一种制备包含索非那新或其盐的组合物的新方法，以及通过该方法制备的包含索非那新或其盐的组合物，其中将任选取代的低级烷基加入到solifenacin的奎宁环的2-位。 本发明的组合物含有高纯度的solifenacin，而对于该方法而言，特别是非常低含量的意想不到的化合物，因此其具有非常优选的作为药物的体积的性质。

公开(公告)号：US07652052B2

公开(公告)日：2010-01-26

申请号：US11918282

申请日：2006-04-10

申请人： Masatoshi Inakoshi ,  Kiyotaka Marumo ,  Noriya Yamamoto ,  Hiroshi Kiyonaga ,  Yasuaki Ohishi

发明人： Masatoshi Inakoshi ,  Kiyotaka Marumo ,  Noriya Yamamoto ,  Hiroshi Kiyonaga ,  Yasuaki Ohishi

IPC分类号： A61K31/416 ,  C07D231/56

CPC分类号： C07D235/06 ,  C07D403/06

摘要： To provide a novel process for producing ramosetron or its salt that is useful as a pharmaceutical, especially as a therapeutic and/or preventive agent for digestive symptoms caused by administration of an anti-malignant tumor agent, diarrheal-type irritable bowel syndrome, diarrheal symptoms of irritable bowel syndrome, etc.Ramosetron or its salt can be produced by reacting a compound of the formula (I): [wherein X is a halogen] or a salt thereof with 1-methyl-1H-indole in the presence of a Lewis acid selected from the group consisting of a lower alkylaluminum dihalide, a di-lower alkylaluminum halide, a tri-lower alkylaluminum and a lower alkylaluminum sesquihalide.

摘要翻译： 提供可用作药物的雷莫司琼或其盐的新方法，特别是作为通过施用抗恶性肿瘤剂引起的消化系统症状的治疗和/或预防剂，腹泻型肠易激综合征，腹泻症状 肠易激综合征等。拉莫司琼或其盐可以通过在路易斯的存在下使式（I）化合物：[其中X为卤素]或其盐与1-甲基-1H-吲哚反应来制备。 酸选自二卤代低级烷基铝，二低级烷基卤化铝，三低级烷基铝和低级烷基铝倍半卤化物。

公开(公告)号：US20070293690A1

公开(公告)日：2007-12-20

申请号：US11631634

申请日：2005-07-07

申请人： Hiroshi Tomiyama ,  Masayuki Yokota ,  Atsushi Noda ,  Yoshinori Kobayashi ,  Junko Ogasawara ,  Yasumasa Hayashi ,  Masatoshi Inakoshi ,  Hirofumi Nakamura ,  Tokuo Koide ,  Kenichiro Sakamoto ,  Yohei Yamashita ,  Akio Miyafuji ,  Takayuki Suzuki ,  Noriyuki Kawano ,  Junji Miyata ,  Masakazu Imamura ,  Takashi Sugane

发明人： Hiroshi Tomiyama ,  Masayuki Yokota ,  Atsushi Noda ,  Yoshinori Kobayashi ,  Junko Ogasawara ,  Yasumasa Hayashi ,  Masatoshi Inakoshi ,  Hirofumi Nakamura ,  Tokuo Koide ,  Kenichiro Sakamoto ,  Yohei Yamashita ,  Akio Miyafuji ,  Takayuki Suzuki ,  Noriyuki Kawano ,  Junji Miyata ,  Masakazu Imamura ,  Takashi Sugane

IPC分类号： C07D309/02

CPC分类号： C07C49/255 ,  C07C45/48 ,  C07C45/63 ,  C07C45/71 ,  C07C49/245 ,  C07H7/04 ,  C07H15/04

摘要： A process for producing an azulene derivative useful as a Na+-glucose cotransporter inhibitor, which is high in yield, is simple in operation, is low in cost, is suited for environmental protection, and is advantageous industrially, the process being characterized by reducing and deprotecting at least one compound selected from penta-acyl compounds and tetra-acyl compounds or salts thereof to obtain a C-glycoside compound; and a useful intermediate for synthesis of such an azulene derivative, obtained in the course of the above process.

摘要翻译： 制备用作产率高的Na + + - 葡萄糖共转运蛋白抑制剂的薁衍生物的方法操作简单，成本低，适用于环境保护，在工业上有利 该方法的特征在于将至少一种选自五酰基化合物和四酰基化合物或其盐的化合物还原和去保护以获得C-糖苷化合物; 以及在上述方法中获得的这种薁衍生物的合成的有用中间体。

公开(公告)号：US20090069570A1

公开(公告)日：2009-03-12

申请号：US11918282

申请日：2006-04-10

申请人： Masatoshi Inakoshi ,  Kiyotaka Marumo ,  Noriya Yamamoto ,  Hiroshi Kiyonaga ,  Yasuaki Ohishi

发明人： Masatoshi Inakoshi ,  Kiyotaka Marumo ,  Noriya Yamamoto ,  Hiroshi Kiyonaga ,  Yasuaki Ohishi

IPC分类号： C07D235/02

CPC分类号： C07D235/06 ,  C07D403/06

摘要： [Problems] To provide a novel process for producing ramosetron or its salt that is useful as a pharmaceutical, especially as a therapeutic and/or preventive agent for digestive symptoms caused by administration of an anti-malignant tumor agent, diarrheal-type irritable bowel syndrome, diarrheal symptoms of irritable bowel syndrome, etc. [Means for Resolution] Ramosetron or its salt can be produced by reacting a compound of the formula (I): [wherein X is a halogen] or a salt thereof with 1-methyl-1H-indole in the presence of a Lewis acid selected from the group consisting of a lower alkylaluminum dihalide, a di-lower alkylaluminum halide, a tri-lower alkylaluminum and a lower alkylaluminum sesquihalide.

摘要翻译： [问题]提供可用作药物的雷莫司琼或其盐的新方法，特别是作为由施用抗恶性肿瘤剂引起的消化系统症状的治疗和/或预防剂，腹泻型肠易激综合征 肠易激综合征的腹泻症状等[解决方法]拉莫司琼或其盐可以通过使式（I）化合物：其中X为卤素或其盐与1-甲基-1H- 在选自二卤代低级烷基铝，二低级烷基铝卤化物，三低级烷基铝和低级烷基铝倍半卤化物的路易斯酸存在下反应。