公开(公告)号：US07579507B2

公开(公告)日：2009-08-25

申请号：US11871710

申请日：2007-10-12

申请人： Kiyoshi Kasai ,  Takehiro Ishikawa ,  Tetsuji Ozawa ,  Koji Kamata ,  Ritsu Suzuki ,  Hideki Takeuchi

发明人： Kiyoshi Kasai ,  Takehiro Ishikawa ,  Tetsuji Ozawa ,  Koji Kamata ,  Ritsu Suzuki ,  Hideki Takeuchi

IPC分类号： C07C217/14

CPC分类号： C07C217/22 ,  C07B2200/07 ,  C07B2200/13

摘要： Crystals of a salt of 4′-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-3-isopropyl-3′,5′-dimethylbiphenyl-4-carboxylic acid. The α type, β type and γ type crystals produced by treating hydrochloride of 4′-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-3-isopropyl-3′,5′-dimethylbiphenyl-4-carboxylic acid with specified solvents, which can be discriminated by the characteristic diffraction peaks of powder X-ray diffractometry and the like.

摘要翻译： 4' - {2 - [（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基氨基]乙氧基} -3-异丙基-3'，5'-二甲基联苯-4 -羧酸。 通过处理4' - {2 - [（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基氨基]乙氧基} -3-异丙基氢氧化物的盐酸盐制备的α型，β型和γ型晶体 -3'，5'-二甲基联苯-4-羧酸，其特征在于可以通过粉末X射线衍射等的特征衍射峰区分。

公开(公告)号：US20080161294A1

公开(公告)日：2008-07-03

申请号：US11903904

申请日：2007-09-25

申请人： Ritsu Suzuki ,  Kenji Yokoyama ,  Tatsuhiro Kondo ,  Hideaki Hirasawa ,  Mikie Kambara ,  Hiroaki Kobayashi

发明人： Ritsu Suzuki ,  Kenji Yokoyama ,  Tatsuhiro Kondo ,  Hideaki Hirasawa ,  Mikie Kambara ,  Hiroaki Kobayashi

IPC分类号： A61K31/5513 ,  A61P3/10 ,  C07D243/14

CPC分类号： A61K45/06 ,  A61K31/5513 ,  C07D243/14 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D413/10 ,  C07D413/12

摘要： Urea derivatives represented by the following general formula (I): which have an agonism of V2 receptor, are useful as agents for the treatment or prevention of diabetes insipidus, nocturia, nocturnal enuresis, overactive bladder or the like.In the formula, R1 represents a hydrogen atom or a C1-6 alkyl group which may have a substituent, R2 is a hydrogen atom or a C1-6 alkyl group, R3 is a hydrogen atom, a C1-6 alkyl group or the like, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, R7 is a hydrogen atom, a heteroaryl group which may have a substituent, a C3-8 cycloalkyl group, an amino group which may have a substituent or a C1-6 alkoxy group which may have a substituted group, M1 is a single bond, a C1-4 alkylene group or the like, Y is N or CRF (in the formula, and RF represents a hydrogen atom, a C1-6 alkyl group or the like, or pharmaceutically acceptable salts thereof, or prodrugs thereof, or pharmaceutical compositions comprising the same and pharmaceutical uses thereof.

摘要翻译： 由以下通式（I）表示的具有V2受体激动作用的尿素衍生物可用作治疗或预防尿崩症，夜尿症，夜间遗尿症，膀胱过度活动症等的药剂。 在该式中，R 1表示可以具有取代基的氢原子或C 1-6烷基，R 2是氢 原子或C 1-6烷基，R 3是氢原子，C 1-6烷基等，R R 5，R 5和R 6独立地是氢原子，卤素原子等，R 7， 可以具有取代基的杂芳基，C 3-8环烷基，可以具有取代基的氨基或C 1-6烷基， 可以具有取代基的烷氧基，M 1是单键，C 1-4亚烷基等，Y是N或CRF （在该式中，R“F”表示氢原子，C 1-6烷基等，或其药学上可接受的盐或前体药物 或其药物组合物及其药物用途。

公开(公告)号：US20080076826A1

公开(公告)日：2008-03-27

申请号：US11871710

申请日：2007-10-12

申请人： Kiyoshi KASAI ,  Takehiro ISHIKAWA ,  Tetsuji OZAWA ,  Koji KAMATA ,  Ritsu SUZUKI ,  Hideki TAKEUCHI

发明人： Kiyoshi KASAI ,  Takehiro ISHIKAWA ,  Tetsuji OZAWA ,  Koji KAMATA ,  Ritsu SUZUKI ,  Hideki TAKEUCHI

IPC分类号： A61K31/195 ,  C07C63/33

CPC分类号： C07C217/22 ,  C07B2200/07 ,  C07B2200/13

摘要： Crystals of a salt of 4′-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-3-isopropyl-3′, 5′-dimethylbiphenyl-4-carboxylic acid. The α type, β type and γ type crystals produced by treating hydrochloride of 4′-{2-[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl-amino]ethoxy}-3-isopropyl-3′,5′-dimethylbiphenyl-4-carboxylic acid with specified solvents, which can be discriminated by the characteristic diffraction peaks of powder X-ray diffractometry and the like.

摘要翻译： 4' - {2 - [（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基氨基]乙氧基} -3-异丙基-3'，5'-二甲基联苯-4 -羧酸。 通过处理4' - {2 - [（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基 - 氨基]乙氧基} -3的盐酸盐产生的α型，β型和γ型晶体 异丙基-3'，5'-二甲基联苯-4-羧酸与特定的溶剂混合，可以通过粉末X射线衍射等的特征衍射峰区分。

公开(公告)号：US07022689B2

公开(公告)日：2006-04-04

申请号：US10486137

申请日：2002-08-08

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

IPC分类号： A01N43/00 ,  A61K31/33

CPC分类号： C07C311/29

摘要： The present invention relates to a 5-amidino-N-(2-aminophenethyl)-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or a lower alkyl group; R2 represents a hydrogen atom, an optionally substituted lower alkyl group, etc.; R3 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group, etc., or a pharmaceutically acceptable salt thereof, which exerts a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-N-（2-氨基苯乙基）-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或低级烷基; R 2表示氢原子，任选取代的低级烷基等; R 3是二（低级烷基）氨基，低级烷基，环烷基等; Q是氢原子或任意取代的低级烷基; Z是氢原子或羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗发生相关疾病的药剂 活化凝血因子X，包含其的药物组合物，其药物用途和其中间体。

公开(公告)号：US07423185B2

公开(公告)日：2008-09-09

申请号：US10545380

申请日：2004-01-30

申请人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

发明人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

IPC分类号： C07C217/14 ,  C07C217/20 ,  C07D307/79 ,  A61K31/195 ,  A61P1/00 ,  A61P1/16 ,  A61P3/04

CPC分类号： C07D307/79 ,  A61K31/195 ,  C07C217/18 ,  C07C217/20 ,  C07C323/62 ,  C07C2601/04

摘要： The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 and R2 are each hydrogen or lower alkyl; R3, R4, R5 and R6 are each hydrogen, halogen, lower alkyl or lower alkoxy; R7 and R8 are each hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy, cycloalkyl, aryl, heteroaryl, cyano, a hydroxyl group, lower acyl, carboxy or the like; R9 is —C(O)—R10, -A1-C(O)—R10, —O-A2-C(O)—R10 or a tetrazol-5-yl group, which exhibit potent and selective β3-adrenoceptor stimulating 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各自为氢或低级烷基; R 3，R 4，R 5和R 6各自为氢，卤素，低级烷基或低级烷氧基 ; R 7和R 8各自为氢，卤素，低级烷基，卤代低级烷基，低级烷氧基，环烷基，芳基，杂芳基，氰基，羟基，低级酰基 ，羧基等; R 9是-C（O）-R 10，-A 1 -C（O）-R 10 O > - O 2 -C（O）-R 10或四唑-5-基，其显示出有效和选择性的β3肾上腺素受体刺激活性。 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：US20060128807A1

公开(公告)日：2006-06-15

申请号：US10545380

申请日：2004-01-30

申请人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

发明人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

IPC分类号： A61K31/195 ,  C07C229/22

CPC分类号： C07D307/79 ,  A61K31/195 ,  C07C217/18 ,  C07C217/20 ,  C07C323/62 ,  C07C2601/04

摘要： The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 and R2 are each hydrogen or lower alkyl; R3, R4, R5 and R6 are each hydrogen, halogen, lower alkyl or lower alkoxy; R7 and R8 are each hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy, cycloalkyl, aryl, heteroaryl, cyano, a hydroxyl group, lower acyl, carboxy or the like; R9 is —C(O)—R10, -A1-C(O)—R10, —O-A2-C(O)—R10 or a tetrazol-5-yl group, which exhibit potent and selective β3-adrenoceptor stimulating 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各自为氢或低级烷基; R 3，R 4，R 5和R 6各自为氢，卤素，低级烷基或低级烷氧基 ; R 7和R 8各自为氢，卤素，低级烷基，卤代低级烷基，低级烷氧基，环烷基，芳基，杂芳基，氰基，羟基，低级酰基 ，羧基等; R 9是-C（O）-R 10，-A 1 -C（O）-R 10 O > - O 2 -C（O）-R 10或四唑-5-基，其显示出有效和选择性的β3肾上腺素受体刺激活性。 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：US07674938B2

公开(公告)日：2010-03-09

申请号：US11936680

申请日：2007-11-07

申请人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

发明人： Junichi Kobayashi ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

IPC分类号： C07C217/14 ,  C07C217/20 ,  C07D307/79 ,  A61K31/195 ,  A61P1/16 ,  A61P3/04

CPC分类号： C07D307/79 ,  A61K31/195 ,  C07C217/18 ,  C07C217/20 ,  C07C323/62 ,  C07C2601/04

摘要： The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 and R2 are each hydrogen or lower alkyl; R3, R4, R5 and R6 are each hydrogen, halogen, lower alkyl or lower alkoxy; R7 and R8 are each hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy, cycloalkyl, aryl, heteroaryl, cyano, a hydroxyl group, lower acyl, carboxy or the like; R9 is —C(O)—R10, -A1-C(O)—R10, —O-A2-C(O)—R10 or a tetrazol-5-yl group, which exhibit potent and selective β3-adrenoceptor stimulating 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各自为氢或低级烷基; R3，R4，R5和R6各自为氢，卤素，低级烷基或低级烷氧基; R 7和R 8各自为氢，卤素，低级烷基，卤代低级烷基，低级烷氧基，环烷基，芳基，杂芳基，氰基，羟基，低级酰基，羧基等; R9是-C（O）-R10，-A1-C（O）-R10，-O-A2-C（O）-R10或四唑-5-基，其表现出有效和选择性的3-肾上腺素受体 刺激活动。 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：US20080249177A1

公开(公告)日：2008-10-09

申请号：US11936680

申请日：2007-11-07

申请人： Junichi KOBAYASHI ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

发明人： Junichi KOBAYASHI ,  Tetsuya Nakamura ,  Ritsu Suzuki ,  Hideyuki Muranaka ,  Tomonaga Ozawa ,  Yuichiro Kai ,  Takehiro Ishikawa ,  Tatsuhiro Kondo ,  Tetsuro Tamai ,  Satoshi Akahane

IPC分类号： A61K31/192 ,  C07C229/00 ,  A61P3/00

CPC分类号： C07D307/79 ,  A61K31/195 ,  C07C217/18 ,  C07C217/20 ,  C07C323/62 ,  C07C2601/04

摘要： The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 and R2 are each hydrogen or lower alkyl; R3, R4, R5 and R6 are each hydrogen, halogen, lower alkyl or lower alkoxy; R7 and R8 are each hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy, cycloalkyl, aryl, heteroaryl, cyano, a hydroxyl group, lower acyl, carboxy or the like; R9 is —C(O)—R10, -A1-C(O)—R10, —O-A2-C(O)—R10 or a tetrazol-5-yl group, which exhibit potent and selective β3-adrenoceptor stimulating 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各自为氢或低级烷基; R 3，R 4，R 5和R 6各自为氢，卤素，低级烷基或低级烷氧基 ; R 7和R 8各自为氢，卤素，低级烷基，卤代低级烷基，低级烷氧基，环烷基，芳基，杂芳基，氰基，羟基，低级酰基 ，羧基等; R 9是-C（O）-R 10，-A 1 -C（O）-R 10 O > - O 2 -C（O）-R 10或四唑-5-基，其显示出有效和选择性的β3肾上腺素受体刺激活性。 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：US20070232594A1

公开(公告)日：2007-10-04

申请号：US11803187

申请日：2007-05-11

申请人： Kenji Yokoyama ,  Ritsu Suzuki ,  Tatsuhiro Kondo ,  Atsushi Kondo ,  Hiroaki Kobayashi

发明人： Kenji Yokoyama ,  Ritsu Suzuki ,  Tatsuhiro Kondo ,  Atsushi Kondo ,  Hiroaki Kobayashi

IPC分类号： A61K31/5513 ,  C07D413/02 ,  C07D243/12

CPC分类号： C07D243/14 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/10 ,  C07D405/04 ,  C07D409/06 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06

摘要： A present invention provides aromatic amide derivatives which have an agonism of V2 receptor, are useful as agents for the treatment or prevention of diabetes insipidus, nocturia, nocturnal enuresis, overactive bladder or the like, and are represented by the general formula (I): wherein R1 represents a hydrogen atom or a C1-6 alkyl group which may have a substituent, R2 is a hydrogen atom or a C1-6 alkyl group, R3 is a hydrogen atom, a C1-6 alkyl group or the like, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, R7 is a hydrogen atom, a heteroaryl group which may have a substituent, a C3-8 cycloalkyl group, an amino group which may have a substituent or a C1-6 alkoxy group which may have a substituted group; M1 is a single bond, a C1-4 alkylene group or the like Y is N or CRF (in the formula, RF represents a hydrogen atom, a C1-6 alkyl group or the like or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or pharmaceutical compositions comprising the same and pharmaceutical uses thereof.

摘要翻译： 本发明提供具有V2受体激动作用的芳香族酰胺衍生物，可用作治疗或预防尿崩症，夜尿症，夜间遗尿，膀胱过度活动症等的药剂，由通式（I）表示： 其中R 1表示氢原子或可具有取代基的C 1-6烷基，R 2是氢原子或 C 1-6烷基，R 3是氢原子，C 1-6烷基等，R“ R 4，R 5和R 6独立地是氢原子，卤素原子等，R 7是氢 原子，可以具有取代基的杂芳基，C 3-8环烷基，可以具有取代基的氨基或C 1-6烷氧基，其中 可以具有取代基; M 1是单键，C 1-4 - 亚烷基等，Y是N或CR F（在式中，R F代表氢原子，C 1-6烷基等或其药学上可接受的盐，或其前药，或其药物组合物和药物组合物 其用途。

公开(公告)号：US20090030218A1

公开(公告)日：2009-01-29

申请号：US11914915

申请日：2006-05-17

申请人： Kiyoshi Kasai ,  Minoru Kubota ,  Ritsu Suzuki ,  Tetsuji Ozawa ,  Takehiro Ishikawa ,  Makoto Kobayashi ,  Junichi Sonehara ,  Masahiro Kobayashi

发明人： Kiyoshi Kasai ,  Minoru Kubota ,  Ritsu Suzuki ,  Tetsuji Ozawa ,  Takehiro Ishikawa ,  Makoto Kobayashi ,  Junichi Sonehara ,  Masahiro Kobayashi

IPC分类号： C07D303/40 ,  C07C69/76 ,  C07C229/38 ,  C07C255/00

CPC分类号： C07D303/22 ,  C07B53/00 ,  C07C67/08 ,  C07C67/31 ,  C07C69/94 ,  C07C213/06 ,  C07C253/30 ,  C07C255/54 ,  C07C217/22

摘要： The present invention provides an industrial method for preparing aminoalcohol derivatives (I) having a biphenyl group, biphenyloxyacetaldehyde derivatives which are used therefore, preparing methods thereof, and intermediates used for the preparing method.The present invention also provides a preparing method including processes for preparing a 3-substituted biphenylcarboxylic acid derivative represented by the following general formula: by allowing a 3-fluorobiphenylcarboxylic acid derivative prepared from a 3-fluorobiphenylcarbonitrile derivative which can be prepared by allowing a 4-halophenol derivative to react with a 2-fluorobenzonitrile derivative which is substituted by a leaving group at 4-position to react with an organometallic reagent.

摘要翻译： 本发明提供了制备具有联苯基的氨基醇衍生物（I）的工业方法，因此使用的联苯氧基乙醛衍生物及其制备方法以及用于制备方法的中间体。 本发明还提供了一种制备方法，其包括由以下通式表示的3-取代的联苯基羧酸衍生物的制备方法：通过使由3-氟联苯基腈衍生物制备的3-氟联苯基羧酸衍生物，其可以通过使4- 卤代酚衍生物与在4-位上被离去基团取代的2-氟苄腈衍生物反应，与有机金属试剂反应。