公开(公告)号：US06376707B1

公开(公告)日：2002-04-23

申请号：US09889857

申请日：2001-07-23

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

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

IPC分类号： C07C22900

CPC分类号： C07C217/60 ,  C07C213/10

摘要： 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.

摘要翻译： 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：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。

公开(公告)号：US07208520B2

公开(公告)日：2007-04-24

申请号：US10489343

申请日：2002-08-27

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

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

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

CPC分类号： A61K31/216 ,  C07B2200/07 ,  C07C217/60

摘要： 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.

摘要翻译： 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：US20090062518A1

公开(公告)日：2009-03-05

申请号：US11908693

申请日：2006-03-16

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

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

IPC分类号： C07H1/00

CPC分类号： C07H17/02

摘要： 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.

摘要翻译： 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

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

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

IPC分类号： C07H17/02 ,  A61K31/7056

CPC分类号： C07H17/02

摘要： 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.

摘要翻译： 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：US20090069421A1

公开(公告)日：2009-03-12

申请号：US11912407

申请日：2006-04-24

申请人： Kiyoshi Kasai ,  Michio Toda

发明人： Kiyoshi Kasai ,  Michio Toda

IPC分类号： A61K31/216 ,  C07C229/34 ,  A61P13/00

CPC分类号： C07C217/60

摘要： The present invention provides a novel crystal polymorph of ethyl (−)-2-[4-[2-[[1S,2R]-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-2,5-dimethylphenoxyacetate hydrochloride which can be determined by characteristic diffraction peaks of the powder X-ray diffraction or the like, and obtained from ethyl (−)-2-[4-[2-[[1S,2R]-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-2,5-dimethylphenoxyacetate by a specific method.

摘要翻译： 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] 可以通过粉末X射线衍射等的特征衍射峰确定，并由（ - ） - 2- [4- [2 - [[1S，2R] -2- 羟基-2-（4-羟基苯基）-1-甲基乙基]氨基]乙基] -2,5-二甲基苯氧基乙酸酯。

公开(公告)号：US07763654B2

公开(公告)日：2010-07-27

申请号：US11912407

申请日：2006-04-24

申请人： Kiyoshi Kasai ,  Michio Toda

发明人： Kiyoshi Kasai ,  Michio Toda

IPC分类号： A61K31/24 ,  C07C229/00

CPC分类号： C07C217/60

摘要： The present invention provides a novel crystal polymorph of ethyl (−)-2-[4-[2-[[1S,2R]-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-2,5-dimethylphenoxyacetate hydrochloride which can be determined by characteristic diffraction peaks of the powder X-ray diffraction or the like, and obtained from ethyl (−)-2-[4-[2-[[1S,2R]-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-2,5-dimethylphenoxyacetate by a specific method.

摘要翻译： 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] 可以通过粉末X射线衍射等的特征衍射峰确定，并由（ - ） - 2- [4- [2 - [[1S，2R] -2- 羟基-2-（4-羟基苯基）-1-甲基乙基]氨基]乙基] -2,5-二甲基苯氧基乙酸酯。

公开(公告)号：US08703289B2

公开(公告)日：2014-04-22

申请号：US11588388

申请日：2006-10-27

申请人： Kouji Tamori ,  Tetsuo Fukuta ,  Mitsuhiro Murata ,  Masaru Ueno ,  Satoshi Katayose ,  Eiji Takamoto ,  Kiyoshi Kasai

发明人： Kouji Tamori ,  Tetsuo Fukuta ,  Mitsuhiro Murata ,  Masaru Ueno ,  Satoshi Katayose ,  Eiji Takamoto ,  Kiyoshi Kasai

IPC分类号： B32B5/16 ,  A61K9/14

CPC分类号： G01N33/54326 ,  C08F8/36 ,  C08F8/42 ,  C08F8/44 ,  C08F220/26 ,  C08F220/32 ,  C08F222/1006 ,  C08F257/02 ,  C08F265/04 ,  C08F291/00 ,  C08F2810/20 ,  C08L25/04 ,  C08L33/066 ,  C08L51/003 ,  G01N33/5434 ,  H01F1/0054 ,  Y10T428/2991 ,  Y10T428/2998 ,  C08L2666/06 ,  C08L2666/02 ,  C08F8/12 ,  C08F2220/325 ,  C08F2220/1825 ,  C08F2222/1013 ,  C08F212/08 ,  C08F212/36 ,  C08F220/14 ,  C08F2222/1026 ,  C08F2220/281 ,  C08F2220/282

摘要： The organic polymer particles comprise a carboxyl group and 2,3-dihydroxypropyl group, and the magnetic particles for diagnostics comprise fine magnetic material particles and a polymer part containing a hydrophilic polymer part and a crosslinked polymer part, a dry coating film obtained from a water dispersion thereof having a contact angle with water of 5° to 60°. The process for producing the carboxyl group-containing particles comprises a step of producing an ester bond by reacting a hydroxyl group in organic polymer particles having the hydroxyl group with a carboxylic anhydride. The organic polymer particles comprise a hydroxyl group originating from a 2,3-dihydroxypropyl group and a polyoxyethylene group.

摘要翻译： 有机聚合物颗粒包含羧基和2,3-二羟基丙基，用于诊断的磁性颗粒包括细小的磁性材料颗粒和含有亲水性聚合物部分和交联聚合物部分的聚合物部分，从水中获得的干燥涂膜 其与水的接触角为5°至60°的分散体。 制备含羧基颗粒的方法包括通过使具有羟基的有机聚合物颗粒中的羟基与羧酸酐反应而产生酯键的步骤。 有机聚合物颗粒包含源自2,3-二羟基丙基和聚氧乙烯基团的羟基。

公开(公告)号：US4716028A

公开(公告)日：1987-12-29

申请号：US829171

申请日：1986-02-14

申请人： Kiyoshi Kasai ,  Takaaki Tsukidate ,  Toshihiko Arakawa

发明人： Kiyoshi Kasai ,  Takaaki Tsukidate ,  Toshihiko Arakawa

IPC分类号： C01B21/068 ,  C04B35/584 ,  C01B33/06

CPC分类号： C04B35/584 ,  C01B21/068 ,  C01P2002/04 ,  C01P2004/62 ,  C01P2006/10

摘要： A high .alpha.-type silicon nitride powder is prepared by thermally decomposing a mixture of a crystalline silicon nitride powder having an oxygen content of at least 1.0% by weight and a nitrogen-containing silane compound.

摘要翻译： 通过将氧含量为至少1.0重量％的结晶氮化硅粉末和含氮硅烷化合物的混合物热分解来制备高α型氮化硅粉末。

公开(公告)号：US4694035A

公开(公告)日：1987-09-15

申请号：US823013

申请日：1986-01-27

申请人： Kiyoshi Kasai ,  Masayuki Hattori ,  Osamu Kikuchi ,  Hiromi Takeuchi ,  Haruhiro Hirai ,  Nobuo Sakurai

发明人： Kiyoshi Kasai ,  Masayuki Hattori ,  Osamu Kikuchi ,  Hiromi Takeuchi ,  Haruhiro Hirai ,  Nobuo Sakurai

IPC分类号： C08F2/00 ,  C08F2/18 ,  C08F257/02 ,  C08F291/00

CPC分类号： C08F257/02 ,  C08F291/00

摘要： A process for preparing large-sized polymer particles having a particle diameter in a range of 0.1 to 500 .mu.m by seeded polymerization is described, comprising:finely dispersing a polymerizable monomer in an aqueous medium to prepare a monomer dispersion in which a number average particle diameter of the resulting monomer droplets is not larger than that of seed particles, and a number average particle diameter in a semi-stable condition (Dm) of the monomer droplets satisfies, with a desired number average particle diameter of the final polymer particle as D, the following relation:0.5.times.D

摘要翻译： 描述了通过接种聚合制备粒度在0.1至500μm范围内的大尺寸聚合物颗粒的方法，其包括：将可聚合单体细分散在水性介质中以制备单体分散体，其中数均粒子 所得单体液滴的直径不大于种子颗粒的直径，并且单体液滴的半稳定条件（Dm）中的数均粒径满足所需的最终聚合物颗粒的数均粒径为D 以下关系：将所述单体分散体与种子颗粒的分散体组合以使可聚合单体吸收或吸附在种子颗粒上的0.5×D < 并在聚合引发剂的存在下聚合可聚合单体。