公开(公告)号：US06755075B2

公开(公告)日：2004-06-29

申请号：US09958477

申请日：2001-11-21

申请人： Nobuo Nagashima ,  Kensuke Miyahara ,  Saburo Matsuoka

发明人： Nobuo Nagashima ,  Kensuke Miyahara ,  Saburo Matsuoka

IPC分类号： G01N348

CPC分类号： G01Q60/366 ,  G01N3/42 ,  G01N2203/0286 ,  G01N2203/0647 ,  Y10S977/852

摘要： An ultra micro indentation testing apparatus comprises: a lever stand provided with a center lever having a silicon probe and a diamond indenter disposed therein; a moving mechanism for moving the lever stand in a triaxial direction; in indentation mechanism for pushing the diamond indenter in a sample; a displacement gage for measuring a displacement of the silicon probe or the diamond indenter; and an optical picture device for positioning the silicon probe or the diamond indenter and observing the surface of the sample. The apparatus has, in combination, a hardness measuring function based on the measurement of the force and depth of the diamond indenter pushed in the surface of the sample, an atomic force microscopic function of acquiring the shape of the surface of the sample based on a displacement of the diamond indenter or the silicon probe, and an optical microscopic function of observing the surface of the sample by the optical picture device. Furthermore, the testing apparatus is equipped with both the function of measuring the hardness of the surface of material in a ultra micro region and the surface observing function with high accuracy.

摘要翻译： 超微压痕测试装置包括：杆架，设置有具有硅探针和设置在其中的金刚石压头的中心杆; 用于使杆架沿三轴方向移动的移动机构; 用于将金刚石压头推入样品的压痕机构; 用于测量硅探针或金刚石压头的位移的位移计; 以及用于定位硅探针或金刚石压头并观察样品表面的光学图像装置。 该装置组合地具有基于在样品表面推动的金刚石压头的力和深度的测量的硬度测量功能，基于样品的表面获取样品的形状的原子力显微镜功能 金刚石压头或硅探针的位移，以及通过光学图像装置观察样品表面的光学显微镜功能。 此外，测试装置既具有测量超微区域中的材料表面的硬度和高精度的表面观察功能的功能。

公开(公告)号：US06457349B1

公开(公告)日：2002-10-01

申请号：US09647099

申请日：2000-11-20

申请人： Kensuke Miyahara ,  Saburo Matsuoka ,  Nobuo Nagashima

发明人： Kensuke Miyahara ,  Saburo Matsuoka ,  Nobuo Nagashima

IPC分类号： G02N330

CPC分类号： G01N3/48 ,  G01N2203/0082 ,  G01N2203/0286 ,  Y10S977/852

摘要： A testing method is provided for determining the hardness of a micro region, using indentation curves indicating relations between observed penetration depths and indenting forces when an arbitrary shaped indenter is pushed into standard samples of plural types. The method involves (1) measuring relations between observed penetration depths and indenting forces when the arbitrary shaped indenter is pushed into standard samples of plural types, to prepare the indentation curves, (2) determining a reference function indicative of macro hardness, by standardizing the relations between the indenting forces and macro hardness at the same penetration depth as an index, for the indentation curves of the standard samples of plural types, (3) measuring a relation between the penetration depth and indenting force of an arbitrary sample, and (4) determining the hardness of a micro region from the measured value in step (3) according to the reference function as determined in step (2).

摘要翻译： 提供了一种用于确定微区域的硬度的测试方法，使用指示当任意形状的压头被压入多种类型的标准样品时观察到的穿透深度和压痕力之间的关系的压痕曲线。 该方法包括（1）当将任意形状的压头推入多种类型的标准样品时测量观察到的穿透深度和压痕力之间的关系，以制备压痕曲线，（2）通过标准化标准化来确定指示宏观硬度的参考功能 对于多种类型的标准样品的压痕曲线，（3）测量任意样品的穿透深度和压痕力之间的关系，以及（4）的断裂力与相同穿透深度的宏观硬度之间的关系为 ）根据步骤（2）中确定的参考函数从步骤（3）中的测量值确定微区域的硬度。

公开(公告)号：US20110305595A1

公开(公告)日：2011-12-15

申请号：US13203102

申请日：2010-01-29

申请人： Saburo Matsuoka ,  Masao Hayakawa ,  Etsuo Takeuchi ,  Nobuo Nagashima

发明人： Saburo Matsuoka ,  Masao Hayakawa ,  Etsuo Takeuchi ,  Nobuo Nagashima

IPC分类号： C22C38/04 ,  C22C38/14 ,  C22C38/12 ,  C22C38/02 ,  C22C38/06

CPC分类号： H01M8/04208 ,  C21D8/005 ,  C21D9/14 ,  C21D2211/005 ,  C22C38/02 ,  C22C38/04 ,  C22C38/12 ,  C22C38/14 ,  H01M8/04201 ,  Y02P70/56

摘要： A ferritic steel having tensile properties and fatigue properties capable of withstanding use in a hydrogen environment and a method of manufacture thereof are provided. By adding one or more element selected from among vanadium (V), titanium (Ti) and niobium (Nb) so that the steel includes, together with at least ferrite grains in the structure, a carbide or carbides of one or more element selected from among V, Ti and Nb, the reduction of area and the fatigue crack propagation rate of the ferritic steel in a hydrogen environment are improved. The advantages of the invention were confirmed in cases where the ferrite grains are small grains of 1 μm or less in size, and in cases where the ferrite grains are coarse grains from several micrometers to 20 μm in size, and moreover in cases where the ferrite grains are coarse grains from several micrometers to 60 μm in size.

摘要翻译： 提供一种具有耐氢气环境中使用的拉伸性能和疲劳特性的铁素体钢及其制造方法。 通过添加选自钒（V​​），钛（Ti）和铌（Nb）中的一种或多种元素，使得钢至少与结构中的铁素体晶粒一起包含一种或多种元素的碳化物或碳化物， 在V，Ti和Nb中，在氢环境中铁素体钢的面积减小和疲劳裂纹扩展速率提高。 在铁素体晶粒尺寸小于1μm的小晶粒的情况下，在铁素体晶粒的尺寸为几微米至20μm的粗晶粒的情况下，在铁素体的情况下，在本发明的优点的情况下， 晶粒是尺寸从几微米到60μm的粗晶粒。

公开(公告)号：US07223859B2

公开(公告)日：2007-05-29

申请号：US10801141

申请日：2004-03-16

申请人： Tatsuyoshi Tanaka ,  Masanobu Sugawara ,  Hirofumi Maeda ,  Akira Nishiyama ,  Yoshihiko Yasohara ,  Nobuo Nagashima

发明人： Tatsuyoshi Tanaka ,  Masanobu Sugawara ,  Hirofumi Maeda ,  Akira Nishiyama ,  Yoshihiko Yasohara ,  Nobuo Nagashima

IPC分类号： C07D205/02 ,  C07C233/00

CPC分类号： C07D205/08 ,  C07C231/02 ,  C07C309/66 ,  C07C309/73

摘要： The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

摘要翻译： 本发明提供了一种容易地制备用于药物产品中间体（特别是胆固醇酯转移蛋白（CETP）抑制剂）的（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸酰胺衍生物的方法， 容易获得的原料。 在本发明中，由容易获得的原料制备的（S）-N- [4-（三氟甲基）苯基] -3-羟基戊酸酰胺导致（R）-4-乙基-1- [4-（三氟甲基） ）苯基] -2-氮杂环丁酮，得到（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸酰胺。 此外，将（R）-4-乙基-1- [4-（三氟甲基）苯基] -2-氮杂环丁酮与氨基甲酸酯反应，得到（R）-3- [4-（三氟甲基）苯基氨基] - 戊酸 酰胺衍生物。

公开(公告)号：US5071966A

公开(公告)日：1991-12-10

申请号：US576499

申请日：1990-09-10

申请人： Kazunori Kan ,  Hiroshi Murakami ,  Nobuo Nagashima ,  Noboru Ueyama ,  Takehisa Ohashi

发明人： Kazunori Kan ,  Hiroshi Murakami ,  Nobuo Nagashima ,  Noboru Ueyama ,  Takehisa Ohashi

IPC分类号： C07F7/02 ,  C07F7/18

CPC分类号： C07F7/186 ,  C07F7/1852

摘要： A process for preparing an enol silyl ether compound from a diazoacetoacetic acid ester having the general formula (IV): ##STR1## wherein R.sup.1 is a lower alkyl group having 1 to 6 carbon atoms, phenyl group, a substituted phenyl group, an aralkyl group or allyl group, and R.sup.2, R.sup.3 and R.sup.4 are the same or mutually different and each is a lower alkyl group having 1 to 6 carbon atoms, which comprises reacting a diazoacetoacetic acid ester having the general formula (I): ##STR2## wherein R.sup.1 is the same as defined above, with a trialkylsilyl chloride having the general formula (II): ##STR3## wherein R.sup.2, R.sup.3 and R.sup.4 are the same as defined above, in an inert solvent in the presence of an organic base and an alkali halide having the general formula (III):MX (III)wherein M is an alkaline metal and X is bromine atom or iodine atom. The desired compound is useful as an intermediate for synthesis of carbapenem .beta.-lactam antibiotics.

摘要翻译： PCT No.PCT / JP90 / 00038 Sec。 371 1990年9月10日第 102（e）1990年9月10日PCT 1990年1月12日PCT PCT。 公开号WO90 / 08149 日本时间1990年7月26日。一种由具有通式（IV）的重氮乙酰乙酸酯制备烯醇甲硅烷基醚化合物的方法：其中R 1为具有1至6个碳原子的低级烷基，苯基 基团，取代的苯基，芳烷基或烯丙基，R 2，R 3和R 4相同或相互不同，各自为具有1至6个碳原子的低级烷基，其包括使具有一般性基团的重氮乙酰乙酸酯 式（I）：其中R 1与上述定义相同，具有通式（II）的三烷基甲硅烷基氯：其中R2，R3和R4与上述定义相同 在有机碱和具有通式（III）的碱金属卤化物存在下，在惰性溶剂中反应：其中M是碱金属，X是溴原子或碘原子的MX（III）。 所需化合物可用作合成碳青霉烯β-内酰胺抗生素的中间体。

公开(公告)号：US20100197934A1

公开(公告)日：2010-08-05

申请号：US12757947

申请日：2010-04-09

申请人： Takahiro Ohishi ,  Hirokazu Nanba ,  Masanobu Sugawara ,  Masashi Izumida ,  Tatsuya Honda ,  Kohei Mori ,  Satohiro Yanagisawa ,  Nobuo Nagashima ,  Kenji Inoue

发明人： Takahiro Ohishi ,  Hirokazu Nanba ,  Masanobu Sugawara ,  Masashi Izumida ,  Tatsuya Honda ,  Kohei Mori ,  Satohiro Yanagisawa ,  Nobuo Nagashima ,  Kenji Inoue

IPC分类号： C12P17/10 ,  C12P13/12 ,  C07C321/00 ,  C07D233/02

CPC分类号： C12P13/12 ,  C07C319/06 ,  C07D233/76 ,  C12P17/04 ,  C12P17/10 ,  C12P41/009 ,  C07C323/58

摘要： The present invention provides a simple industrial process for producing an L- or D-optically active α-methylcysteine derivative or its salt, which is a useful pharmaceutical intermediate, from readily available, inexpensive raw materials. In a process for producing an L- or D-optically active α-methylcysteine derivative or its salt, a racemic N-carbamoyl-α-methylcysteine derivative or its salt is D-selectively cyclized with hydantoinase to produce a D-5-methyl-5-thiomethylhydantoin derivative or its salt and an N-carbamoyl-α-methyl-L-cysteine derivative or its salt, which are then subjected to deprotection of the amino group and the sulfur atom, and hydrolysis.

摘要翻译： 本发明提供了一种简单的工业方法，用于从容易获得的便宜的原料制备作为有用的药物中间体的L-或D-光学活性的α-甲基半胱氨酸衍生物或其盐。 在制备L-或D-光学活性α-甲基半胱氨酸衍生物或其盐的方法中，外消旋的N-氨基甲酰基-α-甲基半胱氨酸衍生物或其盐与乙内酰脲酶D选择性环化以产生D-5-甲基 - 5-硫代甲基乙内酰脲衍生物或其盐和N-氨基甲酰基-α-甲基-L-半胱氨酸衍生物或其盐，然后进行氨基和硫原子的脱保护和水解。

公开(公告)号：US20060089503A1

公开(公告)日：2006-04-27

申请号：US10540023

申请日：2003-12-10

申请人： Takahiro Ohishi ,  Kohei Mori ,  Koichi Kinoshita ,  Katsuji Maehara ,  Hiroaki Kawasaki ,  Nobuo Nagashima ,  Yoshihide Fuse

发明人： Takahiro Ohishi ,  Kohei Mori ,  Koichi Kinoshita ,  Katsuji Maehara ,  Hiroaki Kawasaki ,  Nobuo Nagashima ,  Yoshihide Fuse

IPC分类号： C07D305/12 ,  C07D405/02

CPC分类号： C07D305/12 ,  C07C319/14 ,  C07D317/60 ,  C07D407/06 ,  C07C323/56

摘要： The present invention provides a process for simply producing an optically active 2-thiomethyl-3-phenylpropionic acid derivative useful as an intermediate for medicines from inexpensive raw materials. An optically active 2-hydroxymethyl-3-phenylpropionic acid ester derivative which can be relatively easily obtained by asymmetric reduction reaction with an enzyme is cyclized to an optically active P-lactone derivative which is then reacted with a sulfur compound to produce an optically active 2-thiomethyl-3-phenylpropionic acid derivative in high yield.

摘要翻译： 本发明提供简单地生产用作廉价原料的药物中间体的光学活性2-硫代甲基-3-苯基丙酸衍生物的方法。 可以通过与酶的不对称还原反应相对容易地获得的光学活性的2-羟甲基-3-苯基丙酸酯衍生物环化成光学活性的P-内酯衍生物，然后与硫化合物反应以产生光学活性2 硫代甲基-3-苯基丙酸衍生物。

公开(公告)号：US06515179B2

公开(公告)日：2003-02-04

申请号：US10148877

申请日：2002-06-11

申请人： Nobuo Nagashima

发明人： Nobuo Nagashima

IPC分类号： C07D20716

CPC分类号： C07D207/416 ,  C07C209/62 ,  C07C213/02 ,  C07C227/18 ,  C07C269/04 ,  C07D205/04 ,  C07C211/27 ,  C07C229/36 ,  C07C271/20

摘要： A 2- or 4-nitrobenzenesulfonamide is allowed to react with an alkali metal alkoxide to remove a nitrobenzenesulfonyl group to thereby obtain an amine corresponding to the amide. Furthermore, a method for producing an amine derivative by allowing the resulting amine without isolation to react with an activated, substituted oxycarbonyl compound or an activated acyl compound is provided. According to this method, a corresponding free amine and its substituted derivative can be produced easily and industrially advantageously from the 2- or 4-nitrobenzenesulfonamide without using a thiol compound.

摘要翻译： 使2-或4-硝基苯磺酰胺与碱金属醇盐反应以除去硝基苯磺酰基，从而得到对应于酰胺的胺。 此外，提供了通过使得到的胺不经分离而与活化的取代的氧羰基化合物或活化的酰基化合物反应来制备胺衍生物的方法。 根据该方法，可以在不使用硫醇化合物的情况下，容易且工业上有利地从2-或4-硝基苯磺酰胺制备相应的游离胺及其取代的衍生物。

公开(公告)号：US20100048909A1

公开(公告)日：2010-02-25

申请号：US12227788

申请日：2007-05-22

申请人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

发明人： Kohei Mori ,  Akira Nishiyama ,  Naoaki Taoka ,  Daisuke Moriyama ,  Nobuo Nagashima

IPC分类号： C07D263/12 ,  C07D303/38 ,  C07C237/06

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C67/31 ,  C07C231/18 ,  C07C237/04 ,  C07C237/22 ,  C07C2601/02 ,  C07D263/16 ,  C07D301/24 ,  C07D303/16 ,  C07D303/48 ,  C12P7/42 ,  C12P13/02 ,  C12P41/002 ,  C07C69/675

摘要： An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.

公开(公告)号：US07408084B2

公开(公告)日：2008-08-05

申请号：US10516469

申请日：2003-06-02

申请人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C07C211/05 ,  C07C213/08

CPC分类号： C07C49/84 ,  C07B2200/07 ,  C07C45/63 ,  C07C213/00 ,  C07C215/28 ,  C07C221/00 ,  C07C215/30 ,  C07C225/16

摘要： A process for easily producing an optically active β-amino alcohol useful as a pharmaceutical intermediate from an inexpensive, readily available starting material is provided. A readily available α-substituted ketone is reacted with an optically active amine to yield a diastereomer mixture of an optically active α-substituted aminoketone. One of the diastereomers is isolated optionally after the diastereomers are converted to salts with an acid. The optically active α-substituted aminoketone or a salt thereof thus isolated was stereoselectively reduced to yield an optically active β-substituted amino alcohol. The optically active β-substituted amino alcohol is subjected to hydrogenolysis to produce an optically active β-amino alcohol or a salt thereof.

摘要翻译： 提供了一种从便宜的，容易获得的起始材料中容易地生产用作药物中间体的光学活性β-氨基醇的方法。 将容易获得的α-取代的酮与光学活性胺反应，得到光学活性的α-取代的氨基酮的非对映异构体混合物。 在非对映异构体与酸转化成盐之后，任选地分离非对映异构体之一。 将如此分离的光学活性α-取代的氨基酮或其盐立体选择性地还原，得到光学活性的β-取代的氨基醇。 将光学活性的β-取代氨基醇进行氢解以产生光学活性的β-氨基醇或其盐。