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1. 发明申请

US20070010689A1 Optically active 3,3'-dithiobis(2-amino-2methylpropionic acid) derivative and process for producing optically active 2-amino-3-mercapto-2-methylpropionic acid derivative 审中-公开
标题翻译：光活性的3,3'-二硫代双（2-氨基-2-甲基丙酸）衍生物和光学活性2-氨基-3-巯基-2-甲基丙酸衍生物的制备方法
公开(公告)号：US20070010689A1
公开(公告)日：2007-01-11
申请号：US10570791
申请日：2004-08-18
申请人： Shingo Matsumoto , Hiroshi Murao , Takao Yamaguchi , Masashi Izumida , Yasuyoshi Ueda
发明人： Shingo Matsumoto , Hiroshi Murao , Takao Yamaguchi , Masashi Izumida , Yasuyoshi Ueda
IPC分类号： C07C323/50
CPC分类号： C07D403/12 , C07B2200/07 , C07C319/06 , C07C323/58 , C07D233/76 , C12P7/52 , C12P11/00 , C12P41/002
摘要： The present invention provides a useful novel intermediate and a novel synthetic process that can highly prevent contamination by various impurities to an optically active R or S isomer of a 2-amino-3-mercapto-2-methylpropionic acid derivative or salt thereof useful as an intermediate for pharmaceuticals and the like and provides a process for easily and efficiently producing a high purity optically active R or S isomer of a 2-amino-3-mercapto-2-methylpropionic acid derivative or salt thereof on an industrial production scale. A process of producing a high purity 2-amino-3-mercapto-2-methylpropionic acid derivative or salt thereof includes reductively cleaving a sulfur-sulfur bond of an intermediate, which is a high purity optically active 3,3′-dithiobis(2-amino-2-methylpropionic acid) derivative substantially free of impurities. Thus, a resulting optically active 2-amino-3-mercapto-2-methylpropionic acid derivative can be produced without generating impurities as by-products which are difficult to remove.
摘要翻译：本发明提供了一种有用的新型中间体和新型合成方法，其可以高度防止各种杂质污染2-氨基-3-巯基-2-甲基丙酸衍生物的光学活性R或S异构体或其盐，其用作药物等的中间体，并且以工业生产规模提供容易且有效地制备2-氨基-3-巯基-2-甲基丙酸衍生物或其盐的高纯度光学活性R或S异构体的方法。制备高纯度2-氨基-3-巯基-2-甲基丙酸衍生物或其盐的方法包括还原性地裂解作为高纯度光学活性3,3'-二硫代双（2）的中间体的硫 - 硫键 - 氨基-2-甲基丙酸）衍生物。因此，得到的光学活性2-氨基-3-巯基-2-甲基丙酸衍生物可以不产生作为难以除去的副产物的杂质。

2. 发明授权

US06400517B1 Magnetic media processing device 有权
标题翻译：磁介质处理装置
公开(公告)号：US06400517B1
公开(公告)日：2002-06-04
申请号：US09617244
申请日：2000-07-14
申请人： Hiroshi Murao
发明人： Hiroshi Murao
IPC分类号： G11B2504
CPC分类号： G06K7/084
摘要： A magnetic media processing device including an encoder for producing an output for a predetermined distance in a conveyance distance of a magnetic media on conveyance, a road circuit device for reading magnetic data stored in the magnetic media in synchronizing the output from the encoder to be processed as to its waveforms to produce read data, and an arithmetic device for converting a data length to data of a distance based on a time component of a data length of the read data of the read circuit device by employing the output signal from the encoder to read data based on distance data, wherein the arithmetic device compensates the process delay time in a time component of read data produced from the read circuit device when the arithmetic device converts the data length into the data of distance.
摘要翻译：一种磁性介质处理装置，包括：编码器，用于在输送时在磁性介质的输送距离内产生预定距离的输出;轨道电路装置，用于读取存储在磁性介质中的磁数据，同步来自待处理编码器的输出关于其产生读取数据的波形，以及运算装置，用于根据读取电路装置的读取数据的数据长度的时间分量将数据长度转换成距离的数据，方法是使用来自编码器的输出信号基于距离数据读取数据，其中当运算装置将数据长度转换成距离的数据时，运算装置补偿从读取电路装置产生的读取数据的时间分量中的处理延迟时间。

3. 发明授权

US07307184B2 Processes for preparing oxazolidinone derivatives of β-hydroxyethlamine compounds and for preparing β-hydroxyethlamine compounds 失效
标题翻译：制备β-羟基三甲基胺化合物的恶唑烷酮衍生物和制备β-羟基三甲基胺化合物的方法
公开(公告)号：US07307184B2
公开(公告)日：2007-12-11
申请号：US10478439
申请日：2002-05-23
申请人： Hiroshi Murao , Koki Yamashita , Toshihiro Takeda , Yasuyoshi Ueda
发明人： Hiroshi Murao , Koki Yamashita , Toshihiro Takeda , Yasuyoshi Ueda
IPC分类号： C07C269/00 , C07C269/06
CPC分类号： C07D263/24 , C07D263/22
摘要： The present invention provides a process of starting from N-alkoxycarbonyl-ethylamine compounds having a leaving group at the β-position to prepare oxazolidinone derivatives of β-hydroxyethylamine compounds having an inverted steric configuration at the β-position carbon, which comprises introducing a step of treating in contact with water with heating under acidic to neutral conditions into the process. Also, the present invention provides a process of starting from N-alkoxycarbonyl-ethylamine compounds having a leaving group at the β-position to prepare β-hydroxyethylamine compounds having an inverted steric configuration at the β-position carbon, which comprises subjecting the oxazolidinone derivatives prepared as described above to a step of treating in contact with water under basic conditions.
摘要翻译：本发明提供了从在β-位上具有离去基团的N-烷氧基羰基 - 乙胺化合物开始以制备β-位羟基化合物的恶唑烷酮衍生物的方法，所述β-羟乙基胺化合物在β-位置碳具有反向立体构型，其包括引入步骤在酸性到中性条件下加热处理与水接触。此外，本发明提供了从在β-位上具有离去基团的N-烷氧基羰基 - 乙胺化合物开始以制备在β-位置碳具有反向立体构型的β-羟乙基胺化合物的方法，该方法包括使恶唑烷酮衍生物如上所述制备成在碱性条件下与水接触的步骤。

4. 发明申请

US20060135784A1 PROCESS FOR PRODUCING 3-AMINO-2-HYDROXYPROPIONIC ACID DERIVATIVES 审中-公开
标题翻译：生产3-氨基-2-羟基丙酸衍生物的方法
公开(公告)号：US20060135784A1
公开(公告)日：2006-06-22
申请号：US11276222
申请日：2006-02-17
申请人： Hiroshi MURAO , Koki Yamashita , Toshihiro Takeda , Yasuyoshi Ueda
发明人： Hiroshi MURAO , Koki Yamashita , Toshihiro Takeda , Yasuyoshi Ueda
IPC分类号： C07D263/38 , C07D263/04
CPC分类号： C07D263/20 , C07C227/20 , C07C227/32 , C07C227/42 , Y02P20/55 , C07C229/22 , C07C229/34
摘要： The present invention provides a process for preparing 3-amino-2-hydroxypropionic acid derivatives (1) which does not use dangerous reagents, is economically advantageous, and is suitable for an industrial production, which process comprises: treating N-protected-3-amino-2-hydroxypropionic acid derivatives (2) having a steric configuration at 2-position carbon reverse to that of derivatives (1) with a leaving group-introducing agent to convert into N-protected-3-aminopropionic acid derivatives (3), then treating the derivatives with a basic substance to convert into substituted-3-amino-2-hydroxypropionic acid derivatives (4) having an inverted steric configuration at 2-position carbon, and then converting the derivatives into 3-amino-2-hydroxypropionic acid derivatives (1).
摘要翻译：本发明提供了一种制备不使用危险试剂的3-氨基-2-羟基丙酸衍生物（1）的方法，在经济上是有利的，适用于工业生产，该方法包括：将N-保护的3- 具有与衍生物（1）相反的2-位碳位置的氨基-2-羟基丙酸衍生物（2）与离去基团引入剂转化为N-保护的3-氨基丙酸衍生物（3），然后用碱性物质处理衍生物，将其转化成在2-位碳上具有反向立体构型的取代-3-氨基-2-羟基丙酸衍生物（4），然后将其转化为3-氨基-2-羟基丙酸衍生物（1）。

5. 发明授权

US6011170A Process for producing of cysteine derivatives 失效
标题翻译：半胱氨酸衍生物的制备方法
公开(公告)号：US6011170A
公开(公告)日：2000-01-04
申请号：US142688
申请日：1999-04-22
申请人： Takeshi Kondo , Akira Nishiyama , Noboru Ueyama , Hiroshi Murao , Hajime Manabe , Yasuyoshi Ueda
发明人： Takeshi Kondo , Akira Nishiyama , Noboru Ueyama , Hiroshi Murao , Hajime Manabe , Yasuyoshi Ueda
IPC分类号： C07C319/14 , C07C323/58 , C07C323/59 , C07C321/04
CPC分类号： C07C319/14 , C07B2200/07 , Y02P20/55
摘要： This invention relates to a method comprising reacting an amino acid derivative of the following general formula (I); ##STR1## (wherein R.sup.1 represents an amino-protective group; R.sup.0 represents hydrogen or, taken together with R.sup.1, represents an amino-protecting group; R.sup.2 represents a carboxy-protecting group; X represents a leaving group) with a thiol compound of the following general formula (II):R.sup.3 SH (II)(wherein R.sup.3 represents an alkyl group of 1 to 7 carbon atoms, an aryl group of 6 to 10 carbon atoms, or an aralkyl group of 7 to 10 carbon atoms) to give a cysteine derivative of the following general formula (III): ##STR2## (wherein R.sup.0, R.sup.1, R.sup.2, and R.sup.3 are as defined above), wherein the reaction is conducted in the presence of a base and water in an organic reaction solvent.
摘要翻译： PCT No.PCT / JP98 / 00101 Sec。 371日期1999年4月22日 102（e）日期1999年4月22日PCT提交1998年1月14日PCT公布。第WO98 / 30538号公报日期：1998年7月16日本发明涉及使下述通式（I）的氨基酸衍生物反应的方法。（其中R 1表示氨基保护基; R 0表示氢或与R 1一起表示氨基保护基; R 2表示羧基保护基; X表示离去基团）与下列通式的硫醇化合物反应（II）：R3SH（II）（其中R3表示1〜7个碳原子的烷基，6〜10个碳原子的芳基或7〜10个碳原子的芳烷基），得到以下通式（III）：（其中R 0，R 1，R 2和R 3如上定义），其中反应在有机反应溶剂中在碱和水的存在下进行。

6. 发明申请

US20090069538A1 Method of Producing Peptide 有权
标题翻译：生产肽的方法
公开(公告)号：US20090069538A1
公开(公告)日：2009-03-12
申请号：US12224543
申请日：2006-07-31
申请人： Hiroshi Murao , Ken-ichiro Morio , Masaru Mitsuda
发明人： Hiroshi Murao , Ken-ichiro Morio , Masaru Mitsuda
IPC分类号： C07K1/02 , C07K1/14
CPC分类号： C07K1/061 , C07K1/02 , C07K1/14 , C07K5/06078 , C07K5/06095 , C07K5/0806 , C07K5/0808 , C07K5/101
摘要： The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active ester of an acid component is decreased to 1% or less in a liquid phase peptide synthesis method. According to the invention, a target peptide of high purity can be simply and efficiently produced by a continuous liquid phase synthesis method. Further, the present invention is related to a method of producing a peptide, characterized in using an amide-type solvent immiscible with water in a liquid phase peptide synthesis method. According to the invention, various peptides can be produced by the liquid phase synthesis method without being restricted by the amino acid sequence of the target peptide.
摘要翻译：本发明涉及一种生产肽的方法，其特征在于在缩合反应之后将反应混合物与碱反应以在碱性条件保持下进行水解，直到酸组分的剩余未反应的活性酯的比例降低至在液相肽合成方法中为1％以下。根据本发明，可以通过连续液相合成法简单有效地制备高纯度的靶肽。此外，本发明涉及一种制备肽的方法，其特征在于在液相肽合成方法中使用与水不混溶的酰胺型溶剂。根据本发明，可以通过液相合成法制备各种肽，而不受目标肽的氨基酸序列的限制。

7. 发明授权

US06372941B1 Processes for producing &bgr;-halogeno-&agr;-amino-carboxylic acids and phenylcysteine derivatives and intermediates thereof 失效
标题翻译：制备β-卤代-α-氨基 - 羧酸和苯基半胱氨酸衍生物的方法及其中间体
公开(公告)号：US06372941B1
公开(公告)日：2002-04-16
申请号：US09582461
申请日：1999-08-16
申请人： Koki Yamashita , Kenji Inoue , Koichi Kinoshita , Yasuyoshi Ueda , Hiroshi Murao
发明人： Koki Yamashita , Kenji Inoue , Koichi Kinoshita , Yasuyoshi Ueda , Hiroshi Murao
IPC分类号： C07C22900
CPC分类号： C07C227/16 , C07C319/14 , Y02P20/55 , C07C323/58 , C07C323/59 , C07C229/20
摘要： An industrially advantageous method of producing &bgr;-halogeno-&agr;-aminocarboxylic acids is provided. Methods are also provided of producing optically active N-protected-S-phenylcysteines having high optical purity and of intermediates thereof, respectively, in which the above production method is utilized. A method of producing &bgr;-halogeno-&agr;-aminocarboxylic acids or salts thereof is disclosed which comprises halogenating the hydroxyl group of a &bgr;-hydroxy-&agr;-aminocarboxylic acid (in which the basicity of the amino group in &agr;-position is not masked by the presence of a substituent on said amino group) or a salt thereof with an acid with a halogenating agent. A method of producing optically active N-protected-S-phenylcysteines represented by the general formula (3) or salts thereof is further disclosed which comprises applying the above production method to optically active serine or a salt thereof and then carrying out treatment with an amino-protecting agent and reaction with thiophenol under a basic condition.
摘要翻译：提供了产生β-卤代-α-氨基羧酸的工业上有利的方法。还提供了分别制备具有高光学纯度的光学活性N-保护的S-苯基半胱氨酸及其中间体的方法，其中使用上述制备方法.1。制备β-卤代-α-氨基羧酸或其盐的方法其中包括将β-羟基-α-氨基羧酸的羟基（其中在所述氨基上不存在取代基的α-位置上的氨基的碱性）或其盐与卤素化反应具有卤化剂的酸。进一步公开了制备由通式（3）表示的光学活性N-保护的S-苯基半胱氨酸或其盐的方法，其包括将上述制备方法应用于光学活性丝氨酸或其盐，然后用氨基保护剂和与苯硫酚在基本条件下的反应。

8. 发明授权

US06344572B1 Processes for the preparation of threo-1,2-epoxy-3-amino-4-phenylbutane derivatives 有权
标题翻译：制备苏式-1,2-环氧-3-氨基-4-苯基丁烷衍生物的方法
公开(公告)号：US06344572B1
公开(公告)日：2002-02-05
申请号：US09647340
申请日：2000-11-17
申请人： Katsuji Maehara , Yukinori Tokuda , Hiroshi Murao , Yasuyoshi Ueda
发明人： Katsuji Maehara , Yukinori Tokuda , Hiroshi Murao , Yasuyoshi Ueda
IPC分类号： C07D30102
CPC分类号： C07D301/26 , C07D303/36
摘要： The present invention provides a production method of high quality threo-1,2-epoxy-3-amino-4-phenylbutane derivatives (1) on a commercial scale in a simple, easy and efficient manner and with very high productivity, which comprises treating a threo-1-halo-2-hydroxy-3-amino-4-phenylbutane derivative (2) with a base in a polar organic solvent or a solvent composed of a polar organic solvent and water, and adding the resulting reaction mixture to water to thereby cause the resulting threo-1,2-epoxy-3-amino-4-phenylbutane derivative (1) to crystallize out.
摘要翻译：本发明以简单，容易和有效的方式以非常高的生产率提供了高质量的threo-1,2-epoxy-3-氨基-4-苯基丁烷衍生物（1）的制备方法，其包括处理在极性有机溶剂或由极性有机溶剂和水组成的溶剂中的碱，将苏-1-卤代-2-羟基-3-氨基-4-苯基丁烷衍生物（2）与碱反应，并将得到的反应混合物加入到水从而使得到的所述苏-12-环氧-3-氨基-4-苯基丁烷衍生物（1）结晶出来。

9. 发明授权

US06320072B1 Method for isolation of n-protected s-phenylcysteine 失效
标题翻译：用于分离正保护的S-苯基半胱氨酸的方法
公开(公告)号：US06320072B1
公开(公告)日：2001-11-20
申请号：US09646702
申请日：2000-12-14
申请人： Yasuyoshi Ueda , Hiroshi Murao , Koki Yamashita , Koichi Kinoshita
发明人： Yasuyoshi Ueda , Hiroshi Murao , Koki Yamashita , Koichi Kinoshita
IPC分类号： C07C32100
CPC分类号： C07C319/28 , Y02P20/55 , C07C323/59
摘要： This invention provides a method of isolating N-protected-S-phenylcysteine (1) of high purity, expediently, efficiently and in good yield, which comprises causing said N-protected-S-phenylcysteine to be salted out in the form of a base salt in the presence of water. wherein R1 represents an amino-protecting group; R2 represents a hydrogen atom or, either independently of R1 or taken together with R1, represents an amino-protecting group.
摘要翻译：本发明提供了一种方法，有效和高效分离高纯度N-保护的S-苯基半胱氨酸（1）的方法，其包括使所述N-保护的S-苯基半胱氨酸以碱的形式盐析盐，其中R 1表示氨基保护基; R 2表示氢原子，或独立地为R 1或与R 1一起表示氨基保护基。

10. 发明授权

US08716439B2 Method of producing peptide 有权
标题翻译：生产肽的方法
公开(公告)号：US08716439B2
公开(公告)日：2014-05-06
申请号：US12224543
申请日：2006-07-31
申请人： Hiroshi Murao , Ken-ichiro Morio , Masaru Mitsuda
发明人： Hiroshi Murao , Ken-ichiro Morio , Masaru Mitsuda
IPC分类号： A61K38/00
CPC分类号： C07K1/061 , C07K1/02 , C07K1/14 , C07K5/06078 , C07K5/06095 , C07K5/0806 , C07K5/0808 , C07K5/101
摘要： The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active ester of an acid component is decreased to 1% or less in a liquid phase peptide synthesis method. According to the invention, a target peptide of high purity can be simply and efficiently produced by a continuous liquid phase synthesis method. Further, the present invention is related to a method of producing a peptide, characterized in using an amide-type solvent immiscible with water in a liquid phase peptide synthesis method. According to the invention, various peptides can be produced by the liquid phase synthesis method without being restricted by the amino acid sequence of the target peptide.
摘要翻译：本发明涉及一种生产肽的方法，其特征在于在缩合反应之后将反应混合物与碱反应以在碱性条件保持下进行水解，直到酸组分的剩余未反应的活性酯的比例降低至在液相肽合成方法中为1％以下。根据本发明，可以通过连续液相合成法简单有效地制备高纯度的靶肽。此外，本发明涉及一种制备肽的方法，其特征在于在液相肽合成方法中使用与水不混溶的酰胺型溶剂。根据本发明，可以通过液相合成法制备各种肽，而不受目标肽的氨基酸序列的限制。

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