公开(公告)号：US08680120B2

公开(公告)日：2014-03-25

申请号：US13387266

申请日：2010-07-26

申请人： Kazuya Tatani ,  Naohiro Kawamura ,  Tatsuhiro Kondo ,  Atsushi Kondo

发明人： Kazuya Tatani ,  Naohiro Kawamura ,  Tatsuhiro Kondo ,  Atsushi Kondo

IPC分类号： A61K31/444 ,  A61K31/4439 ,  C07D401/14 ,  C07D401/06 ,  C07D401/04 ,  C07D209/08 ,  C07D209/10 ,  C07D405/06 ,  C07D405/14 ,  C07D405/04

CPC分类号： C07D209/08 ,  C07D209/10 ,  C07D209/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/14 ,  C07D409/04 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14

摘要： A compound (I) of the present invention, which has an EP1 receptor antagonism: [wherein A represents a benzene ring or the like; Y1 represents a C1-6 alkylene group; Y2 represents a single bond or the like; R1 represents a hydrogen atom, a C1-6 alkyl group or the like; R2 represents a phenyl group which may have a substituent, a 5-membered aromatic heterocyclic ring which may have a substituent, a 6-membered aromatic heterocyclic ring which may have a substituent or the like; R3 represents a halogen atom, a C1-6 alkoxy group or the like; R4 represents a hydrogen atom or the like; and R5 represents a hydrogen atom or the like] or a pharmaceutically acceptable salt thereof is provided. Furthermore, the compound (I) of the present invention can be used as an agent for treating or preventing LUTS, in particular, various symptoms of OABs.

摘要翻译： 具有EP1受体拮抗作用的本发明化合物（I）：其中A表示苯环等; Y1表示C1-6亚烷基; Y2表示单键等; R1表示氢原子，C1-6烷基等; R2表示可以具有取代基的苯基，可以具有取代基的5元芳香族杂环，可以具有取代基的6元芳族杂环等; R3表示卤素原子，C1-6烷氧基等; R4表示氢原子等; 并且R5表示氢原子等]或其药学上可接受的盐。 此外，本发明的化合物（I）可以用作治疗或预防LUTS，特别是OAB的各种症状的药剂。

公开(公告)号：US08354382B2

公开(公告)日：2013-01-15

申请号：US12988273

申请日：2009-04-13

申请人： Hideki Takeuchi ,  Eiji Tsuru

发明人： Hideki Takeuchi ,  Eiji Tsuru

IPC分类号： A01N43/04 ,  A61K31/70 ,  C07G3/00 ,  C07H15/00 ,  C07H17/00 ,  C07H17/02 ,  C07H23/00

CPC分类号： C07H17/02

摘要： The present invention provides a novel form of 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide with improved storage stability. Since 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}-propylamino)-2,2-dimethylpropionamide hemifumarate dihydrate has extremely excellent storage stability, it is useful as a drug substance. Furthermore, it shows an extremely good crystalline property and can be purified by a convenient method, and therefore is suitable for the industrial preparation.

摘要翻译： 本发明提供3-（3- {4- [3-（＆bgr。-D-吡喃葡萄糖氧基）-5-异丙基-1H-吡唑-4-基甲基] -3-甲基苯氧基}丙基氨基） 具有改善的储存稳定性的2-二甲基丙酰胺。 由于3-（3- {4- [3-（＆bgr。-D-吡喃葡萄糖氧基）-5-异丙基-1H-吡唑-4-基甲基] -3-甲基苯氧基} - 丙基氨基）-2,2-二甲基丙酰胺半富马酸盐二水合物具有 极好的储存稳定性，作为药物有用。 此外，其显示出非常好的结晶性，并且可以通过方便的方法进行纯化，因此适用于工业制备。

公开(公告)号：US20120064154A1

公开(公告)日：2012-03-15

申请号：US13288348

申请日：2011-11-03

申请人： Tsuyoshi NAGANUMA ,  Mitsuo MURAMATSU

发明人： Tsuyoshi NAGANUMA ,  Mitsuo MURAMATSU

IPC分类号： A61K31/4045 ,  A61P13/00 ,  A61K9/48

CPC分类号： A61K9/1623 ,  A61K9/1652 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/4866 ,  A61K31/4045

摘要： The present invention provides a solid oral dosage form pharmaceutical for the treatment of dysuria, which comprises, as an active ingredient, an indoline compound having an α1-adrenoceptor blocking activity and represented by the formula: prodrug, pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof, wherein said pharmaceutical is prepared to have 85% dissolution time of not more than 60 minutes in a dissolution test according to method 2 (paddle method) of Japanese pharmacopoeia in a condition using water.

摘要翻译： 本发明提供了用于治疗排尿困难的固体口服剂型药物，其包含作为活性成分的具有α1-肾上腺素能受体阻断活性的二氢吲哚化合物，由下式表示：前药，药学上可接受的盐或其药学上可接受的溶剂合物 其中，所述药物在使用水的条件下，根据日本药典的方法2（桨法）在溶出试验中的85％溶解时间为60分钟以下。

公开(公告)号：US20110207935A1

公开(公告)日：2011-08-25

申请号：US13124345

申请日：2009-10-14

申请人： Kazuo Shimizu ,  Masato Iizuka ,  Hideki Fujikura ,  Yasushi Takigawa ,  Masahiro Hiratochi

发明人： Kazuo Shimizu ,  Masato Iizuka ,  Hideki Fujikura ,  Yasushi Takigawa ,  Masahiro Hiratochi

IPC分类号： C07D215/52 ,  C07D277/56 ,  C07D263/34 ,  C07D275/03 ,  C07D285/08 ,  C07D271/06 ,  C07C255/57 ,  C07D231/14 ,  C07D213/79

CPC分类号： C07C255/57 ,  A61K31/192 ,  A61K31/415 ,  A61K31/426 ,  A61K31/44 ,  A61K31/47 ,  C07C255/54 ,  C07D213/79 ,  C07D215/50 ,  C07D231/14 ,  C07D277/20 ,  C07D277/56

摘要： The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal plasma uric acid level and the like. The present invention relates to fused ring derivatives represented by the following formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of plasma uric acid level, prodrugs thereof, salts thereof or the like. In the formula (I), X1 and X2 represent CH or N; ring U represents aryl or heteroaryl; m represents integral number from 0 to 2; n represents integral number from 0 to 3; R1 represents a hydroxy group, amino or C1-6 alkyl; R2 represents C1-6 alkyl, C1-6 alkoxy C1-6 alkyl or the like.

摘要翻译： 本发明提供了可用作预防或治疗与异常血浆尿酸水平等相关的疾病的药剂的化合物。 本发明涉及具有黄嘌呤氧化酶抑制活性的由下式（I）表示的稠环衍生物，可用作预防或治疗与血浆尿酸水平异常有关的疾病，其前药，其盐或类似物 。 在式（I）中，X 1和X 2表示CH或N; 环U表示芳基或杂芳基; m表示0〜2的整数; n表示0〜3的整数; R1表示羟基，氨基或C1-6烷基; R 2表示C 1-6烷基，C 1-6烷氧基C 1-6烷基等。

公开(公告)号：US20110092509A1

公开(公告)日：2011-04-21

申请号：US12526298

申请日：2009-08-07

申请人： Mamoru Kobayashi ,  Tetsuya Asari ,  Mariko Tadachi

发明人： Mamoru Kobayashi ,  Tetsuya Asari ,  Mariko Tadachi

IPC分类号： A61K31/5377 ,  A61K31/165 ,  A61K31/4453 ,  A61P27/02

CPC分类号： A61K31/165 ,  A61K31/4453 ,  A61K31/5375

摘要： The present invention provides pharmaceutical compositions for the prevention or treatment of diseases associated with decrease in tear.The present invention provides pharmaceutical compositions for the prevention or treatment of diseases associated with decrease in tear such as dry eye, dry disorders of cornea and conjunctiva, disorders of the keratoconjunctival epithelium, syndrome with decrease in tear secretion, xerophthalmia, dry eye due to aging, ophthalmopathy in Stevens-Johnson syndrome, ophthalmopathy in Sjögren's syndrome, keratoconjunctival ulcer, dryness in wearing of contact lens or the like, which comprises as an active ingredient a phenylethanolaminotetralin-carboxamide derivative represented by the general formula (I) wherein A represents a lower alkylene group, B represents an amino group, a di(lower alkyl)amino group or a 3 to 7-membered alicyclic amino group which may have an oxygen atom in the ring, a carbon atom with the mark “*” represents a carbon atom of S-configuration or R-configuration, or a mixture thereof and a carbon atom with (S) represents a carbon atom of S-configuration, or a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明提供了用于预防或治疗与泪液减少相关的疾病的药物组合物。 本发明提供了用于预防或治疗与泪液减少相关的疾病的药物组合物，例如干眼症，角膜和结膜的干性失调，角膜结膜上皮的病症，泪液分泌减少的综合征，干眼症，老化造成的干眼症 ，史蒂文森 - 约翰逊综合征中的眼病，西格伦综合征的眼病，角膜结膜溃疡，隐形眼镜等的磨损，其包含作为活性成分的由通式（I）表示的苯基乙酰氨基四氢化萘 - 甲酰胺衍生物，其中A表示低级 亚烷基，B表示氨基，二（低级烷基）氨基或在环中可具有氧原子的3〜7元脂环族氨基，具有标记“*”的碳原子表示碳原子 的S-构型或R构型，或其混合物和碳原子与（S）表示S-构型的碳原子，或者是Phar 其药学上可接受的盐。

公开(公告)号：US07888382B2

公开(公告)日：2011-02-15

申请号：US11918654

申请日：2006-04-18

申请人： Yuji Kiyono ,  Yoshio Okubo ,  Katsumi Hontani ,  Imao Mikoshiba ,  Kazuma Ojima

发明人： Yuji Kiyono ,  Yoshio Okubo ,  Katsumi Hontani ,  Imao Mikoshiba ,  Kazuma Ojima

IPC分类号： A01N43/38 ,  A01N33/02

CPC分类号： C07D209/44 ,  A61K31/133 ,  A61K31/33 ,  A61K31/4035 ,  A61K45/06 ,  A61K2300/00

摘要： For controlling the condition of type 2 diabetes, a pharmaceutical including a combination of mitiglinide, a pharmacologically acceptable salt thereof or a hydrate thereof and an α-glucosidase inhibitor such as voglibose or acarbose, and a therapeutic method using the pharmaceutical are provided. The pharmaceutical according to the present invention has an extremely strong effect of decreasing a morning fasting blood glucose level, a postprandial blood glucose level and HbA1C of a patient with type 2 diabetes, and can improve glucose spike, insulin resistance and lipid metabolism.

摘要翻译： 为了控制2型糖尿病的病症，提供了包括米格列奈，其药理学上可接受的盐或其水合物和α-葡糖苷酶抑制剂如伏格列波糖或阿卡波糖的组合药物和使用该药物的治疗方法。 根据本发明的药物具有降低早晨空腹血糖水平，餐后血糖水平和2型糖尿病患者的HbA1C的极强作用，并且可以改善葡萄糖刺激，胰岛素抵抗和脂质代谢。

公开(公告)号：US07847107B2

公开(公告)日：2010-12-07

申请号：US12087092

申请日：2006-12-26

申请人： Yoshinori Matsumoto ,  Yuki Takeuchi ,  Hiroyuki Yamamoto

发明人： Yoshinori Matsumoto ,  Yuki Takeuchi ,  Hiroyuki Yamamoto

IPC分类号： C07D209/44

CPC分类号： C07B53/00 ,  C07D209/44

摘要： The present invention is to provide a novel method for producing (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid which is useful as a therapeutic agent for diabetes. The present invention relates to a method for producing (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid, which is characterized in that 2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid is subjected to a catalytic reduction reaction in the presence of an asymmetric catalyst prepared from a pyrrolidinebisphosphine compound (I) represented by the following general formula (I): wherein, R1 represents a linear or branched alkyl group having 1-10 carbon atoms, cycloalkyl group, aralkyl group or aryl group which may respectively have a substituent; and R2 and R3 independently represent an optionally substituted aryl group. The * mark in the pyrrolidine ring shows that the carbon atom at that position has the S configuration, and a rhodium compound.

摘要翻译： 本发明提供可用作糖尿病治疗剂的（2S）-2-苄基-3-（顺式 - 六氢-2-异吲哚基羰基）丙酸的新方法。 本发明涉及（2S）-2-苄基-3-（顺 - 六氢-2-异二氢吲哚基羰基）丙酸的制备方法，其特征在于2-亚苄基-3-（顺式 - 六氢-2-异吲哚基羰基） ）丙酸在由以下通式（I）表示的吡咯烷二膦化合物（I）制备的不对称催化剂存在下进行催化还原反应：其中，R1表示具有1-10个碳原子的直链或支链烷基 原子，环烷基，芳烷基或可分别具有取代基的芳基; 并且R 2和R 3独立地表示任选取代的芳基。 吡咯烷环中的*标记表示该位置的碳原子具有S构型和铑化合物。

公开(公告)号：US20100280083A1

公开(公告)日：2010-11-04

申请号：US12810275

申请日：2008-12-22

申请人： Takehiro Ishikawa ,  Hitoshi Inoue ,  Satoko Kobayashi ,  Masako Yoshida ,  Hiroaki Shiohara ,  Yasunori Ueno ,  Nobuyuki Tanaka

发明人： Takehiro Ishikawa ,  Hitoshi Inoue ,  Satoko Kobayashi ,  Masako Yoshida ,  Hiroaki Shiohara ,  Yasunori Ueno ,  Nobuyuki Tanaka

IPC分类号： A61K31/4245 ,  C07D271/06 ,  C07D413/04 ,  C07D417/10 ,  A61K31/427 ,  A61P25/16

CPC分类号： C07D271/06 ,  C07D413/04 ,  C07D413/10 ,  C07D417/10

摘要： The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 and R2 are each hydrogen, lower acyl, lower alkoxycarbonyl or the like; R3 is halo-lower alkyl, lower acyl, halo-lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted arylcarbonyl, lower alkoxycarbonyl or the like; R4 is lower alkyl, halo-lower alkyl, cycloalkyl, lower alkoxy-lower alkyl or the like, which exhibit potent COMT inhibitory activities. The present invention also provides pharmaceutical compositions containing said compound, and uses thereof.

摘要翻译： 本发明提供由通式（I）表示的化合物或其药学上可接受的盐，其中R 1和R 2各自为氢，低级酰基，低级烷氧基羰基等; 低级酰基，卤代低级烷基羰基，环烷基羰基，任意取代的芳基羰基，低级烷氧基羰基等; R4是表现出强大的COMT抑制活性的低级烷基，卤代低级烷基，环烷基，低级烷氧基 - 低级烷基等。 本发明还提供含有所述化合物的药物组合物及其用途。

公开(公告)号：US07750145B2

公开(公告)日：2010-07-06

申请号：US11719201

申请日：2005-11-17

申请人： Shigeru Yonekubo ,  Nobuhiko Fushimi

发明人： Shigeru Yonekubo ,  Nobuhiko Fushimi

IPC分类号： C07H7/06 ,  A01N43/04 ,  A61K31/70

CPC分类号： A61K45/06 ,  A61K31/404 ,  A61K31/4166 ,  C07D405/04 ,  A61K2300/00

摘要： A compound having an SGLT1 and/or SGLT2 inhibitory activity which is usable as an agent for the prevention or treatment of diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, obesity, etc. It is a 1-substituted-3-(β-D-glycopyranosyl) nitrogen-containing heterocyclic compound represented by the general formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or a solvate thereof; an SGLT inhibitor containing the same; a pharmaceutical composition containing the same and a combination pharmacy of them. In the formula, A represents an alkylene group or alkenylene group; B represents a single bond, —O—, —S— or —NH—; C represents an optionally substituted aryl or heteroaryl group; Q independently represents a carbon atom which a hydrogen atom or a substituent binds to, or a nitrogen atom.

摘要翻译： 具有SGLT1和/或SGLT2抑制活性的化合物，其可用作预防或治疗糖尿病，餐后高血糖，葡萄糖耐量降低，糖尿病并发症，肥胖症等的药剂。它是1-取代-3 - （＆bgr ; D-吡喃葡糖基）含氮杂环化合物或其药学上可接受的盐，或其水合物或溶剂化物; 含有其的SGLT抑制剂; 含有它们的药物组合物和它们的组合药剂。 在该式中，A表示亚烷基或亚烯基; B表示单键，-O - ， - S-或-NH-; C表示任选取代的芳基或杂芳基; Q独立地表示氢原子或取代基结合的碳原子或氮原子。

公开(公告)号：US07749972B2

公开(公告)日：2010-07-06

申请号：US11816056

申请日：2006-02-14

申请人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

发明人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

IPC分类号： A61K31/70 ,  A01N43/04 ,  C07H17/02

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02

摘要： The present invention provides a compound having an SGLT1 and/or SGLT2 inhibitory activity which is usable as an agent for the prevention or treatment of diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, obesity or the like.It is a 1-substituted-7-(β-D-glycopyranosyloxy)(aza)-indole compound represented by the general formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof: wherein R1 represents a halogen atom or the like; n represents j an integer number from 0 to 3; R2 represents a hydrogen atom or the like; X represents a carbon atom which a hydrogen atom or the like binds to, or a nitrogen atom; Q represents an alkylene group or an alkenylene group each of which may have an oxygen atom or a sulfur atom in the chain; and A represents an aryl or heteroaryl group which may have a substituent.

摘要翻译： 本发明提供具有SGLT1和/或SGLT2抑制活性的化合物，其可用作预防或治疗糖尿病，餐后高血糖症，葡萄糖耐量降低，糖尿病并发症，肥胖症等。 它是由通式（I）表示的1-取代-7 - （＆bgr-D-吡喃葡萄糖基氧基）（氮杂） - 吲哚化合物，其前体药物或其药学上可接受的盐，或其水合物或溶剂化物： 其中R1表示卤素原子等; n表示j为0〜3的整数; R2表示氢原子等; X表示与氢原子等结合的碳原子或氮原子; Q表示可以在链中具有氧原子或硫原子的亚烷基或亚烯基; A表示可以具有取代基的芳基或杂芳基。