公开(公告)号：US06620916B1

公开(公告)日：2003-09-16

申请号：US09068987

申请日：1998-09-25

申请人： Yoshiyuki Takahara ,  Haruya Sato ,  Eiko Hayashi ,  Masanobu Yatagai ,  Manabu Suzuki ,  Tomoyuki Tabata ,  Chieko Ejima

发明人： Yoshiyuki Takahara ,  Haruya Sato ,  Eiko Hayashi ,  Masanobu Yatagai ,  Manabu Suzuki ,  Tomoyuki Tabata ,  Chieko Ejima

IPC分类号： C07K1452

CPC分类号： C07H15/08 ,  A61K38/00 ,  C07H15/04 ,  C07K14/00 ,  C07K14/52 ,  C07K14/55 ,  C07K14/56

摘要： The present invention relates to a modified physiologically active protein, modified physiologically active proteins produced by the process and pharmaceutical compositions containing the same.

摘要翻译： 本发明涉及一种修饰的生理活性蛋白质，通过该方法产生的修饰的生理活性蛋白质和含有它们的药物组合物。

公开(公告)号：US20070032658A1

公开(公告)日：2007-02-08

申请号：US11498752

申请日：2006-08-04

申请人： Takayuki Hamada ,  Masayuki Oshita ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masayuki Oshita ,  Masanobu Yatagai

IPC分类号： C07D213/56 ,  C07C311/45

CPC分类号： C07C233/47 ,  C07C227/34 ,  C07C271/22 ,  C07C229/36

摘要： Optically active diphenylalanine compounds may be conveniently prepared in a good yield by reacting a diphenylalanine compound represented by formula (1) with an optically active amine compound represented by formula (2) in the presence of an organic solvent to give a diastereomeric salt represented by formula (5) and then treating the diastereomeric salt under acidic conditions to give an optically active diphenylalanine compound represented by formula (3): wherein each symbol is as defined in the specification.

摘要翻译： 通过使由式（1）表示的二苯基丙氨酸化合物与由式（2）表示的光学活性胺化合物在有机溶剂的存在下反应，可以以良好的收率方便地制备光活性二苯丙氨酸化合物，得到式 （5），然后在酸性条件下处理非对映体盐，得到由式（3）表示的光学活性二苯丙氨酸化合物：其中每个符号如说明书中所定义。

公开(公告)号：US20100204505A1

公开(公告)日：2010-08-12

申请号：US12766178

申请日：2010-04-23

申请人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

发明人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

IPC分类号： C07C229/52

CPC分类号： C07D239/96 ,  C07C233/87

摘要： The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

摘要翻译： 本发明提供了具有式（5）喹唑啉二酮环的苯丙氨酸衍生物的制备方法，包括使式（1）的酰基苯丙氨酸衍生物与羰基引入试剂反应的步骤， 和邻氨基苯甲酸的衍生物以形成不对称脲中间体; 在碱的存在下使不对称脲中间体转化为式（4）的喹唑啉二酮化合物; 和得到的喹唑啉二酮化合物的N-烷基化喹唑啉二酮环酰胺与N-烷基化剂。 该制造方法是用于生产具有喹唑啉二酮骨架的苯丙氨酸衍生物的工业上适用的方法，其是作为具有α4整联蛋白抑制活性的药物高度有用的化合物。 在式（1）和（5）中，R 1表示具有取代基等的苯基，R 2表示烷基等，R 3表示二烷基氨基等，R 4表示烷基 等等。

公开(公告)号：US07217835B2

公开(公告)日：2007-05-15

申请号：US10937345

申请日：2004-09-10

申请人： Takayuki Hamada ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masanobu Yatagai

IPC分类号： C07C229/00

CPC分类号： C07C227/16 ,  C07C229/36

摘要： The present invention relates to a method of producing a compound represented by the formula [I] or a salt thereof, which comprises reacting a compound represented by the formula [II] or a salt thereof with a compound represented by the formula [III] or a salt thereof, in the presence of a base, in alcohol, and provides a production method of an O-substituted tyrosine compound, which is superior in productivity, versatility and safety, and economically and industrially useful: wherein each symbol is as defined in the specification.

摘要翻译： 本发明涉及制备由式[I]表示的化合物或其盐的方法，该方法包括使式[Ⅱ]表示的化合物或其盐与式[Ⅲ]表示的化合物或式 其盐，在碱的存在下，在醇中，并且提供了生产率，通用性和安全性优异的O取代的酪氨酸化合物的制备方法，并且在经济和工业上有用：其中每个符号如 规格。

公开(公告)号：US6114525A

公开(公告)日：2000-09-05

申请号：US113509

申请日：1998-07-10

申请人： Toshihiro Matsuzawa ,  Tohru Nishiwaki ,  Seiichi Nishi ,  Masanobu Yatagai

发明人： Toshihiro Matsuzawa ,  Tohru Nishiwaki ,  Seiichi Nishi ,  Masanobu Yatagai

IPC分类号： C07D473/18 ,  C07D473/00

CPC分类号： C07D473/00

摘要： A pure (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine is prepared by:suspending or dissolving a mixture comprising (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine and (7-[1'S,2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine in an alcohol or a hydrous alcohol, reacting the resulting suspension or solution with an alkali metal hydroxide or alkoxide, and selectively precipitating crystals of nucleic acid derivatives of formula (I) ##STR1## wherein M represents an alkali metal.

摘要翻译： 通过以下方法制备纯的（ - ） - 9- [1'S，2'R-双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤：悬浮或溶解包含（ - ） - 9- [1'S，2'R- 双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤和（7- [1'S，2'R-双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤在醇或含水醇中反应，使得到的悬浮液或溶液与 碱金属氢氧化物或醇盐，并且选择性地沉淀式（I）的核酸衍生物的晶体，其中M表示碱金属。

公开(公告)号：US20060270869A1

公开(公告)日：2006-11-30

申请号：US11430909

申请日：2006-05-10

申请人： Takayuki Hamada ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masanobu Yatagai

IPC分类号： C07C237/20

CPC分类号： C07C227/20 ,  C07C231/12 ,  C07C229/36 ,  C07C233/47 ,  C07C233/51

摘要： The present invention provides a production method including reacting a diphenylmethylene halide compound represented by the following formula (1) with a malonic acid diester compound represented by the following formula (2) in an organic solvent selected from N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone and N,N-dimethylformamide, in the presence of a base selected from an alkali metal hydride and an alkali metal t-butoxide to give a diester compound represented by the following formula (3), and then subjecting the diester compound to hydrolysis and decarboxylation to give a diphenylalanine compound represented by the following formula (4). According to the present invention, diphenylalanine compound (4) can be obtained industrially advantageously in a high yield. wherein each symbol is as defined in the specification.

摘要翻译： 本发明提供一种制造方法，其特征在于，使下述式（1）表示的二苯基亚甲基卤化物与下述式（2）所示的丙二酸二酯化合物在选自N-甲基-2-吡咯烷酮，N - 乙基-2-吡咯烷酮和N，N-二甲基甲酰胺，在选自碱金属氢化物和碱金属叔丁醇盐的碱存在下，得到下式（3）表示的二酯化合物，然后 二酯化合物进行水解和脱羧，得到由下式（4）表示的二苯丙氨酸化合物。 根据本发明，可以在工业上有利地以高产率获得二苯丙氨酸化合物（4）。 其中每个符号如说明书中所定义。

公开(公告)号：US20050283021A1

公开(公告)日：2005-12-22

申请号：US10937345

申请日：2004-09-10

申请人： Takayuki Hamada ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masanobu Yatagai

IPC分类号： C07C227/16 ,  C07C229/36

CPC分类号： C07C227/16 ,  C07C229/36

摘要： The present invention relates to a method of producing a compound represented by the formula [I] or a salt thereof, which comprises reacting a compound represented by the formula [II] or a salt thereof with a compound represented by the formula [III] or a salt thereof, in the presence of a base, in alcohol, and provides a production method of an O-substituted tyrosine compound, which is superior in productivity, versatility and safety, and economically and industrially useful: wherein each symbol is as defined in the specification.

摘要翻译： 本发明涉及制备由式[I]表示的化合物或其盐的方法，该方法包括使式[Ⅱ]表示的化合物或其盐与式[Ⅲ]表示的化合物或式 其盐，在碱的存在下，在醇中，并且提供了生产率，通用性和安全性优异的O取代的酪氨酸化合物的制备方法，并且在经济和工业上有用：其中每个符号如 规格。

公开(公告)号：US20050065368A1

公开(公告)日：2005-03-24

申请号：US10934724

申请日：2004-09-07

申请人： Masanobu Yatagai ,  Masafumi Minomura ,  Shigekatsu Tsuchiya

发明人： Masanobu Yatagai ,  Masafumi Minomura ,  Shigekatsu Tsuchiya

IPC分类号： C07C51/41 ,  C07C51/43 ,  C07C51/487 ,  C07C61/04

CPC分类号： C07C51/43 ,  C07B2200/07 ,  C07C51/412 ,  C07C51/487 ,  C07C2601/02 ,  C07C61/04

摘要： The invention provides a process for producing optically active 2,2-dimethylcyclopropanecarboxylic acid by reacting an optical isomer mixture of 2,2-dimethylcyclopropanecarboxylic acid with an optically inactive amine to form (precipitate, crystallize or the like) an ammonium salt of optically active 2,2-dimethylcyclopropanecarboxylic acid, for example, optically active (S)-(+)-2,2-dimethylcyclopropanecarboxylic acid. The production (optical resolution, separation of an optically active substance, purification of an optically active substance or the like) of optically active 2,2-dimethylcyclopropanecarboxylic acid which is important as an intermediate for production of agricultural chemicals, medications and the like can easily be conducted at low cost. Further, the invention provides an intermediate therefor (an ammonium salt of optically active 2,2-dimethylcyclopropanecarboxylic acid, especially preferably an ammonium salt of optically active (S)-(+)-2,2-dimethylcyclopropanecarboxylic acid, or the like), and an optical resolution agent (optically inactive amine) for separation of optically active 2,2-dimethylcyclopropanecarboxylic acid.

摘要翻译： 本发明提供一种通过使2,2-二甲基环丙烷羧酸的光学异构体混合物与光学活性胺反应形成（沉淀，结晶等）光学活性2的铵盐的光学活性2,2-二甲基环丙烷羧酸的方法 ，2-二甲基环丙烷羧酸，例如光学活性（S） - （+） - 2,2-二甲基环丙烷甲酸。 作为农药，药物等的生产中间体重要的光学活性2,2-二甲基环丙烷羧酸的制造（光学拆分，光学活性物质的分离，光学活性物质的纯化等）容易 以低成本进行。 此外，本发明提供了其中间体（光学活性2,2-二甲基环丙烷羧酸的铵盐，特别优选光学活性（S） - （+） - 2,2-二甲基环丙烷甲酸等的铵盐）， 和用于分离光学活性的2,2-二甲基环丙烷羧酸的光学拆分剂（光学惰性胺）。

公开(公告)号：US06346610B1

公开(公告)日：2002-02-12

申请号：US09445240

申请日：1999-12-03

申请人： Noriyasu Kataoka ,  Kenzo Tanaka ,  Masanobu Yatagai

发明人： Noriyasu Kataoka ,  Kenzo Tanaka ,  Masanobu Yatagai

IPC分类号： C07M100

CPC分类号： C07H17/08 ,  Y02P20/55

摘要： An industrially suitable process for preparing V-28-3M useful as an antimycotic agent by conducting methyl esterification of V-28-3 efficiently. V-28-2 is efficiently converted into V-28-3M by protecting the amino group of the amino sugar of V-28-3 with an appropriate protecting group, subjecting the carboxyl group of V-28-3 to methyl esterification with methyl methanesulfonate or methyl p-toluenesulfonate in the presence of a base, and deprotecting the N-protected intermediate.

摘要翻译： 通过有效地进行V-28-3的甲基酯化，可以制备适用于抗真菌剂的V-28-3M的工业上合适的方法。 通过用合适的保护基保护V-28-3的氨基糖的氨基，V-28-2的羧基被甲基酯化，V-28-2被有效地转化成V-28-3M 甲磺酸酯或对甲苯磺酸甲酯在碱的存在下脱保护，并保护N-保护的中间体。

公开(公告)号：US4943652A

公开(公告)日：1990-07-24

申请号：US270514

申请日：1988-11-14

申请人： Masanobu Yatagai ,  Takashi Ohnuki

发明人： Masanobu Yatagai ,  Takashi Ohnuki

IPC分类号： B01J31/14 ,  C07B53/00 ,  C07B61/00 ,  C07C27/00 ,  C07C29/143 ,  C07C31/02 ,  C07C33/26 ,  C07C41/26 ,  C07C43/178 ,  C07C67/00 ,  C07C67/31 ,  C07C69/675 ,  C07C69/732 ,  C07C69/734 ,  C07C231/12 ,  C07C235/06 ,  C07D307/33

CPC分类号： C07C67/31 ,  C07C231/18 ,  C07C29/143 ,  C07C41/26 ,  C07B2200/07

摘要： There is disclosed a process for asymmetrically reducing a carbonyl compound, which comprises reducing the carbonyl compound by the use of a reducing agent comprising (i) an optically active tartaric acid or ester thereof and (ii) a metal borohydride, thereby producing an optically active hydroxyl compound. The process can be used for the production of optically active hydroxyesters and alcohols from ketoesters and ketones. These products are useful for the production of medicaments and liquid crystals.