公开(公告)号：US06376707B1

公开(公告)日：2002-04-23

申请号：US09889857

申请日：2001-07-23

Applicant: Michio Toda ,  Tetsuro Tamai ,  Nobuyuki Tanaka ,  Kiyoshi Kasai ,  Junichi Sonehara ,  Eiji Tsuru

Inventor： Michio Toda ,  Tetsuro Tamai ,  Nobuyuki Tanaka ,  Kiyoshi Kasai ,  Junichi Sonehara ,  Eiji Tsuru

IPC: C07C22900

CPC classification number: C07C217/60 ,  C07C213/10

Abstract: The present invention relates to a crystalline polymorph of 2-[4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxy-phenyl)-1-methylethyl]amino]ethyl]phenoxy]acetic acid having strong diffraction peaks (diffraction angle: 2&thgr;±0.1°) at 10.8, 19.1, 19.3, 19.8, 20.6 and 27.0° in powder X-ray diffraction pattern, which has potent &bgr;2- and &bgr;3-adrenoceptor stimulating effects and is useful as an agent for relieving pain and promoting the removal of calculi in urolithiasis, and the like. For example, the crystalline polymorph can be prepared by hydrolyzing ethyl 2-[4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]-amino]ethyl]phenoxy]acetate phosphate by sodium hydroxide, adding an aqueous phosphoric acid solution at 40° C. and over, adding a mixed solvent of water and methanol or methanol to the resulting compound, and stirring the suspension at 40° C. to reflux temperature for 30 minutes to several hours.

Abstract translation: 本发明涉及2- [4- [2 - [[（1S，2R）-2-羟基-2-（4-羟基 - 苯基）-1-甲基乙基]氨基]乙基]苯氧基]乙酸的结晶多晶型物 在其粉末X射线衍射图中，在10.8,19.1,19.3,19.8,20.6和27.0°处具有强衍射峰（衍射角：2θ±0.1°）的酸，其具有有效的β2-和β3-肾上腺素受体刺激作用，并且是有用的 作为缓解疼痛并促进尿石结石中的结石的去除的药剂等。 例如，结晶多晶型物可以通过水解2- [4- [2 - [[（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基] - 氨基]乙基]苯氧基 ]乙酸磷酸盐与氢氧化钠反应，在40℃加入磷酸水溶液，过滤，向所得化合物中加入水和甲醇或甲醇的混合溶剂，并在40℃下将悬浮液在回流温度下搅拌30 几分钟到几个小时。

公开(公告)号：US20090062518A1

公开(公告)日：2009-03-05

申请号：US11908693

申请日：2006-03-16

Applicant: Kiyoshi Kasai ,  Tetsuji Ozawa ,  Nobuhiko Fushimi ,  Hidetoshi Isawa ,  Ken Kikuchi ,  Masahiro Kobayashi ,  Junichi Sonehara ,  Minoru Kubota

Inventor： Kiyoshi Kasai ,  Tetsuji Ozawa ,  Nobuhiko Fushimi ,  Hidetoshi Isawa ,  Ken Kikuchi ,  Masahiro Kobayashi ,  Junichi Sonehara ,  Minoru Kubota

IPC: C07H1/00

CPC classification number: C07H17/02

Abstract: The present invention relates to a method for preparing the glucopyranosyloxypyrazole derivatives which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications, obesity or the like.A glucopyranosyloxypyrazole derivative can be easily and efficiently prepared by allowing a benzylpyrazole derivative represented by the general formula: wherein R1, R2, R3, R4 and R5 may be the same or different, for example each of them is a hydrogen atom, a halogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, R6 is an alkyl group, for example R7 is a hydrogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, to react with a compound represented by the general formula: wherein as an example, PG1 is a pivaloyl group or the like, as an example, X1 is a bromine atom or the like, therefore the present invention is extremely useful as a method for preparing pharmaceutical compounds.

Abstract translation: 本发明涉及一种制备吡喃葡萄糖氧吡唑衍生物的方法，其可用作预防或治疗与糖尿病，糖尿病并发症，肥胖症等高血糖相关的疾病的药剂。 吡喃葡萄糖氧吡唑衍生物可以容易且有效地制备，其中R 1，R 2，R 3，R 4和R 5可以相同或不同，例如氢原子，卤原子 或烷基，烷氧基，芳基甲氧基等，R6是烷基，例如R7是氢原子或烷基，烷氧基，芳基甲氧基等，与通式表示的化合物反应：其中作为 作为实例，PG1是新戊酰基等，作为实例，X1是溴原子等，因此本发明作为制备药物化合物的方法是非常有用的。

公开(公告)号：US08022192B2

公开(公告)日：2011-09-20

申请号：US11908693

申请日：2006-03-16

Applicant: Kiyoshi Kasai ,  Tetsuji Ozawa ,  Nobuhiko Fushimi ,  Hidetoshi Isawa ,  Ken Kikuchi ,  Masahiro Kobayashi ,  Junichi Sonehara ,  Minoru Kubota

Inventor： Kiyoshi Kasai ,  Tetsuji Ozawa ,  Nobuhiko Fushimi ,  Hidetoshi Isawa ,  Ken Kikuchi ,  Masahiro Kobayashi ,  Junichi Sonehara ,  Minoru Kubota

IPC: C07H17/02 ,  A61K31/7056

CPC classification number: C07H17/02

Abstract: The present invention relates to a method for preparing the glucopyranosyloxypyrazole derivatives which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications, obesity or the like. A glucopyranosyloxypyrazole derivative can be easily and efficiently prepared by allowing a benzylpyrazole derivative represented by the general formula: wherein R1, R2, R3, R4 and R5 may be the same or different, for example each of them is a hydrogen atom, a halogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, R6 is an alkyl group, for example R7 is a hydrogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, to react with a compound represented by the general formula: wherein as an example, PG1 is a pivaloyl group or the like, as an example, X1 is a bromine atom or the like, therefore the present invention is extremely useful as a method for preparing pharmaceutical compounds.

Abstract translation: 本发明涉及一种制备吡喃葡萄糖氧吡唑衍生物的方法，其可用作预防或治疗与糖尿病，糖尿病并发症，肥胖症等高血糖相关的疾病的药剂。 吡喃葡萄糖氧吡唑衍生物可以容易且有效地制备，其中R 1，R 2，R 3，R 4和R 5可以相同或不同，例如氢原子，卤原子 或烷基，烷氧基，芳基甲氧基等，R6是烷基，例如R7是氢原子或烷基，烷氧基，芳基甲氧基等，与通式表示的化合物反应：其中作为 作为实例，PG1是新戊酰基等，作为实例，X1是溴原子等，因此本发明作为制备药物化合物的方法是非常有用的。

公开(公告)号：US20090030218A1

公开(公告)日：2009-01-29

申请号：US11914915

申请日：2006-05-17

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

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

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

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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07208520B2

公开(公告)日：2007-04-24

申请号：US10489343

申请日：2002-08-27

Applicant: Hidetoshi Isawa ,  Yukihiko Hotei ,  Kiyoshi Kasai ,  Junichi Sonehara ,  Satoshi Akahane ,  Hiromu Harada

Inventor： Hidetoshi Isawa ,  Yukihiko Hotei ,  Kiyoshi Kasai ,  Junichi Sonehara ,  Satoshi Akahane ,  Hiromu Harada

IPC: A01N37/12 ,  A01N37/44 ,  A61K31/24

CPC classification number: A61K31/216 ,  C07B2200/07 ,  C07C217/60

Abstract: The present invention provides ethyl (−)-2-[4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-2,5-dimethylphenoxy]acetate hydrochloride, crystalline forms thereof and pharmaceutical compositions containing them, which have excellent β3-adrenoceptor stimulating effects, therapeutic effects on pollakiuria or urinary incontinence and storage stabilities and are useful as a medicament.

Abstract translation: 本发明提供了（ - ） - 2- [4- [2 - [[（1S，2R）-2-羟基-2-（4-羟基苯基）-1-甲基乙基]氨基]乙基] 二甲基苯氧基]乙酸盐酸盐，其结晶形式和含有它们的药物组合物，其具有优异的β3 - 肾上腺素受体刺激作用，对尿频尿失禁和储尿稳定性的治疗作用，并且可用作药物。

公开(公告)号：US20110201793A1

公开(公告)日：2011-08-18

申请号：US13093100

申请日：2011-04-25

Applicant: Kiyoshi KASAI ,  Tetsuji OZAWA ,  Nobuhiko FUSHIMI ,  Hidetoshi ISAWA ,  Ken KIKUCHI ,  Masahiro KOBAYASHI ,  Junichi SONEHARA ,  Minoru KUBOTA

Inventor： Kiyoshi KASAI ,  Tetsuji OZAWA ,  Nobuhiko FUSHIMI ,  Hidetoshi ISAWA ,  Ken KIKUCHI ,  Masahiro KOBAYASHI ,  Junichi SONEHARA ,  Minoru KUBOTA

IPC: C07H17/02

CPC classification number: C07H17/02

Abstract: The present invention relates to a method for preparing the glucopyranosyloxypyrazole derivatives which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications, obesity or the like.A glucopyranosyloxypyrazole derivative can be easily and efficiently prepared by allowing a benzylpyrazole derivative represented by the general formula: wherein R1, R2, R3, R4 and R5 may be the same or different, for example each of them is a hydrogen atom, a halogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, R6 is an alkyl group, for example R7 is a hydrogen atom or an alkyl, alkoxy, arylmethyloxy group or the like, to react with a compound represented by the general formula: wherein as an example, PG1 is a pivaloyl group or the like, as an example, X1 is a bromine atom or the like, therefore the present invention is extremely useful as a method for preparing pharmaceutical compounds.

Abstract translation: 本发明涉及一种制备吡喃葡萄糖氧吡唑衍生物的方法，其可用作预防或治疗与糖尿病，糖尿病并发症，肥胖症等高血糖相关的疾病的药剂。 吡喃葡萄糖氧吡唑衍生物可以容易且有效地制备，其中R 1，R 2，R 3，R 4和R 5可以相同或不同，例如氢原子，卤原子 或烷基，烷氧基，芳基甲氧基等，R6是烷基，例如R7是氢原子或烷基，烷氧基，芳基甲氧基等，与通式表示的化合物反应：其中作为 作为实例，PG1是新戊酰基等，作为实例，X1是溴原子等，因此本发明作为制备药物化合物的方法是非常有用的。