公开(公告)号：US6159974A

公开(公告)日：2000-12-12

申请号：US381829

申请日：1999-09-24

申请人： Yoshihide Ueno ,  Koji Morishita ,  Masami Muraoka ,  Naohito Ohashi

发明人： Yoshihide Ueno ,  Koji Morishita ,  Masami Muraoka ,  Naohito Ohashi

IPC分类号： C07D253/06 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/53 ,  A61P3/06 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D25/22 ,  C07D401/12

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： LDL receptor gene expression promoters containing a 1,2,4-triazine derivative of the formula (I): ##STR1## wherein R.sup.1 is optionally substituted phenyl or heterocycle; R.sup.2 is optionally substituted phenyl, naphthyl, aralkyl, 5- or 6-membered aromatic heterocycle, alkyl, or alkenyl; X is O, S or NR.sup.4 ; R.sup.3 is optionally substituted phenyl, naphthyl, aralkyl, 5- to 6-membered aromatic heterocycle, alkyl, cycloalkyl or alkenyl, provided that when X is NR.sup.4, then it may form an optionally substituted nitrogen-containing heterocycle, or a pharmaceutically acceptable salt thereof, which can increase the expression dose (the amount of mRNA) of LDL receptor gene, and thus increase the amount of LDL receptor, and reduce the serum cholesterol level, and are useful in the treatment of hyperlipidemia.

摘要翻译： PCT No.PCT / JP98 / 01225 Sec。 371 1999年9月24日第 102（e）1999年9月24日PCT PCT 1998年3月23日PCT公布。 公开号WO98 / 42686 日期1998年10月1日含有式（I）的1,2,4-三嗪衍生物的LDL受体基因表达启动子：其中R 1为任选取代的苯基或杂环; R 2是任选取代的苯基，萘基，芳烷基，5或6元芳族杂环，烷基或链烯基; X是O，S或NR4; R3是任选取代的苯基，萘基，芳烷基，5-至6-元芳族杂环，烷基，环烷基或烯基，条件是当X为NR 4时，则其可以形成任选取代的含氮杂环或其药学上可接受的盐 ，这可以增加LDL受体基因的表达剂量（mRNA的量），从而增加LDL受体的量，降低血清胆固醇水平，可用于治疗高脂血症。

公开(公告)号：US4562263A

公开(公告)日：1985-12-31

申请号：US614246

申请日：1984-05-25

申请人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ishizumi

发明人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ishizumi

IPC分类号： C07D209/48 ,  C07D317/60 ,  C07D405/12 ,  C07C99/12

CPC分类号： C07D209/48 ,  C07D317/60 ,  C07D405/12

摘要： A process for producing racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine which comprises phthaloylating the amine group of a racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine derivative to yield a racemic or optically active threo- or erythro-N-phthaloyl-3-(3,4-dihydroxyphenyl)serine derivative and removing the phthaloyl group from the racemic or optically active threo- or erythro-N-phthaloyl-3-(3,4-dihydroxyphenyl)-serine to yield the racemic or optically active threo- or erythro-3-(3,4-dihydroxyphenyl)serine.

摘要翻译： 制备外消旋或光学活性的苏氨酸或赤式3-（3,4-二羟基苯基）丝氨酸的方法，其包括将外消旋或光学活性的苏氨酸或赤式3-（3,4-二羟基苯基）丝氨酸的胺基苯甲酰化 衍生物，得到外消旋或光学活性的苏氨酸或赤式-N-邻苯二甲酰基-3-（3,4-二羟基苯基）丝氨酸衍生物，并从外消旋或光学活性的苏氨酸或赤式-N-邻苯二甲酰基-3- （3,4-二羟基苯基） - 丝氨酸，得到外消旋或光学活性的苏氨酸或赤式3-（3,4-二羟基苯基）丝氨酸。

公开(公告)号：US4480109A

公开(公告)日：1984-10-30

申请号：US455254

申请日：1983-01-03

申请人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ishizumi

发明人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ishizumi

IPC分类号： C07D317/60 ,  C07C19/00 ,  C07D317/54 ,  C07D317/58

CPC分类号： C07D317/60

摘要： A process for producing an optically active threo-3-(3,4-dihydroxyphenyl)serine represented by the formula ##STR1## which is useful as a remedy for peripheral orthostatic hypotension or as an antidepressant, which process comprises treating threo-3-(3,4-methylenedioxyphenyl)serine or an N-carbobenzoxy derivative thereof represented by the formula ##STR2## wherein A represents a hydrogen atom or a carbobenzoxy group, with a Lewis acid to form threo-3-(3,4-dihydroxyphenyl)serine or an N-carbobenzoxy derivative thereof represented by the formula ##STR3## wherein A is as defined above, and, if A is a carbobenzoxy group, catalytically reducing the resulting compound of formula [2]; a racemic or optically active threo-N-carbobenzoxy-3-(3,4-methylenedioxyphenyl)serine represented by the formula ##STR4## which is a novel compound useful as an intermediate in the above synthesis; and a process for producing said novel compound.

摘要翻译： 用于制备由式 [1]表示的光学活性的苏氨酰-3-（3,4-二羟基苯基）丝氨酸的方法，其可用作周围直立性低血压的补救剂或作为抗抑郁药，该方法包括将苏氨酸 - 由式[IMAGE] [3]表示的3-（3,4-亚甲二氧基苯基）丝氨酸或N-苄氧羰基衍生物，其中A表示氢原子或苯甲酰氧基，与路易斯酸形成苏-3-（3 ，4-二羟基苯基）丝氨酸或其通式为“IMAGE”[2]所示的N-苄氧羰基衍生物，其中A如上所定义，如果A为苄氧羰基，则催化还原所得的式[2]化合物。 由上式合成中可用作中间体的新化合物，由式[IMAGE] [3“表示的外消旋或光学活性的苏氨酰-N-苄氧羰基-3-（3,4-亚甲二氧基苯基）丝氨酸; 以及制备所述新型化合物的方法。

公开(公告)号：US4319040A

公开(公告)日：1982-03-09

申请号：US170152

申请日：1980-07-18

申请人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ioshizumi ,  Junki Katsube

发明人： Naohito Ohashi ,  Shoji Nagata ,  Kikuo Ioshizumi ,  Junki Katsube

IPC分类号： C07C227/34 ,  C07C67/00 ,  C07C227/00 ,  C07C227/16 ,  C07C229/36 ,  C07B19/00

CPC分类号： C07C227/34

摘要： Improved process for the production of optical aCTIVE (D- or L-) threo-3-(3,4-dihydroxyphenyl)serine, which comprises subjecting racemic threo-3-(3,4-dibenzyloxyphenyl)-N-carbobenzyloxyserine to optical resolution by using as a resolving reagent an optical active amino alcohol derivative, and then subjecting the resulting optical active (D- or L-) threo-3-(3,4-dibenzyloxyphenyl)-N-carbobenzyloxyserine to hydrogenolysis.

摘要翻译： 制备光学性（D或L-）苏式-3-（3,4-二羟基苯基）丝氨酸的改进方法，其包括使外消旋的3-（3,4-二苄氧基苯基）-N-苄氧基丝氨酸进行光学拆分 通过使用光学活性氨基醇衍生物作为拆分试剂，然后将所得的光学活性（D-或L-）苏-3-（3,4-二苄氧基苯基）-N-苄氧基丝氨酸进行氢解。

公开(公告)号：US07199147B2

公开(公告)日：2007-04-03

申请号：US10480526

申请日：2002-06-06

申请人： Naonori Imazaki ,  Masafumi Kitano ,  Naohito Ohashi ,  Kazuki Matsui

发明人： Naonori Imazaki ,  Masafumi Kitano ,  Naohito Ohashi ,  Kazuki Matsui

IPC分类号： A61K31/415 ,  C07D231/56

CPC分类号： C07D405/12 ,  C07D231/56 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

摘要： A compound represented by the formula (1): wherein R1—X— indicates that 1 to 4 R1—X— groups are present which may be the same or different, the ring A is a saturated or unsaturated 5-membered heterocyclic ring, X is a single bond, a group represented by the formula: —N(R3)—, —O— or —S—, or the like. R1 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, R2 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, and R3 is a hydrogen atom, a substituted or unsubstituted alkyl group, or the like; a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug is a useful compound as a therapeutic agent for diseases for which Rho kinase is responsible.

摘要翻译： 由式（1）表示的化合物：

公开(公告)号：US5648359A

公开(公告)日：1997-07-15

申请号：US365427

申请日：1994-12-28

申请人： Naohito Ohashi ,  Norio Fujiwara ,  Yutaka Ueda

发明人： Naohito Ohashi ,  Norio Fujiwara ,  Yutaka Ueda

IPC分类号： A61K31/445 ,  C07D491/22 ,  A61K31/44 ,  C07D491/153 ,  C07D491/18

CPC分类号： C07D491/22 ,  A61K31/445

摘要： There is provided a composition for inhibiting the production or secretion of tumor necrosis factor effective for the treatment of cachexia, septic shock, multiple organ failure, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, osteoarthritis, Behcet disease, systemic lupus erythematosus (SLE), graft versus host disease (GvHD), malaria, acquired immune deficiency syndrome (AIDS), meningitis, hepatitis and Type II diabetes mellitus. The composition comprises a pharmaceutically effective amount of a compound of formula (1).

摘要翻译： 提供了用于抑制恶性肿瘤，败血性休克，多器官功能衰竭，类风湿性关节炎，炎性肠病，多发性硬化症，骨关节炎，白塞病，系统性红斑狼疮（SLE）等有效治疗肿瘤坏死因子的生成或分泌的组合物。 ，移植物抗宿主病（GvHD），疟疾，获得性免疫缺陷综合征（AIDS），脑膜炎，肝炎和II型糖尿病。 组合物包含药学上有效量的式（1）化合物。

公开(公告)号：US5159089A

公开(公告)日：1992-10-27

申请号：US572122

申请日：1990-08-24

申请人： Naohito Ohashi ,  Koji Fujimoto ,  Yoshihiro Tanaka

发明人： Naohito Ohashi ,  Koji Fujimoto ,  Yoshihiro Tanaka

IPC分类号： C07D303/34 ,  C07D521/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D303/34

摘要： A process for selective production of a threo-epoxy compound of the formula: ##STR1## wherein Ar is a substituted or unsubstituted phenyl group and R.sup.1 and R.sup.2 are each a lower alkyl group, which comprises reacting a ketone compound of the formula: ##STR2## wherein Ar, R.sup.1 and R.sup.2 are each as defined above with a sulfur methylide of the formula: ##STR3## wherein A is a lower alkyl group or a substituted or unsubstituted phenyl group and B is a lower alkyl group, a substituted or unsubstituted phenyl group or a di(lower)-alkylamino group in an aqueous organic solvent.

公开(公告)号：US4540695A

公开(公告)日：1985-09-10

申请号：US407278

申请日：1982-08-11

申请人： Kikuo Ishizumi ,  Naohito Ohashi ,  Michihisa Muramatsu

发明人： Kikuo Ishizumi ,  Naohito Ohashi ,  Michihisa Muramatsu

IPC分类号： C07D235/02 ,  C07D265/12 ,  C07D317/28 ,  C07D413/04 ,  A61K31/13 ,  C07C97/07

CPC分类号： C07D235/02 ,  C07D265/12 ,  C07D317/28 ,  C07D413/04

摘要： Aminonaphthacene derivatives of the formula: ##STR1## wherein A is either one of the following groups: ##STR2## wherein R.sup.1 is a hydrogen atom or a group of the formula: --COR.sup.7, R.sup.2 and R.sup.3 are each a lower alkoxy group or, when taken together, represent an ethylenedioxy group or an oxo group, R.sup.4 and R.sup.5 are both hydrogen atoms or either one of them is a hydrogen atom and the other is a group of the formula: --COR.sup.7, R.sup.6 is a hydrogen atom, a hydroxyl group or a group of the formula: --OCOR.sup.7 and R.sup.7 is a lower alkyl group, a halo(lower)alkyl group, a phenyl group or a halophenyl group, which are useful as anti-microbial and/or anti-tumor agents, or as intermediates in their production.

摘要翻译： 下式的氨基并萘系衍生物：其中A是下列基团之一：其中R 1是氢原子或下式基团-COR 7，R 2和R 3各自是低级烷氧基，或者当 一起代表亚乙二氧基或氧代基，R4和R5都是氢原子，或者它们中的任一个是氢原子，另一个是下式的基团：-COR 7，R 6是氢原子，羟基 或下式的基团：-OCOR 7和R 7是可用作抗微生物和/或抗肿瘤剂的低级烷基，卤代（低级）烷基，苯基或卤代苯基，或作为 中间体在其生产中。

公开(公告)号：US4496739A

公开(公告)日：1985-01-29

申请号：US460797

申请日：1983-01-25

申请人： Naohito Ohashi ,  Kozo Shimago ,  Takaharu Ikeda ,  Kikuo Ishizumi

发明人： Naohito Ohashi ,  Kozo Shimago ,  Takaharu Ikeda ,  Kikuo Ishizumi

IPC分类号： C07D233/32 ,  C07D491/04 ,  C07D491/048 ,  C12N9/18 ,  C12P17/10 ,  C07D233/34

CPC分类号： C07D491/04 ,  C07D233/32 ,  C12N9/18 ,  C12P17/10

摘要： A process for preparing an optically active cis-1,3-dibenzylhexahydro-1H-furo[3,4-d]imidazole-2,4-dione of the formula: ##STR1## wherein an asterisk (*) indicates an asymmetric carbon, Bzl represents a benzyl group and the 3a- and 6a-positions take the cis-configuration, which comprises reducing selectively an optically active cis-imidazolidinedicarboxylic acid monoester of the formula: ##STR2## wherein R is a C.sub.1 -C.sub.6 alkyl group and Bzl is as defined above with a reducing agent at either one of the carboxyl group and the alkoxycarbonyl group in the said monoester, followed by cyclization, the said monoester being the one obtainable by hydrolysis of a cis-imidazolidinedicarboxylic acid diester of the formula: ##STR3## wherein R and Bzl are each as defined above with an enzymatic material having a capability of hydrolyzing the ester group in the said diester.

摘要翻译： 制备下式的光学活性顺式-1,3-二苄基六氢-1H-呋喃并[3,4-d]咪唑-2,4-二酮的方法：其中星号（*）表示 不对称碳，Bzl表示苄基，3a-和6a-位呈顺式构型，其包括选择性地还原下式的光学活性顺式 - 咪唑烷二羧酸单酯：其中R是C1- C6烷基和Bz1如上所定义，在所述单酯中的羧基和烷氧基羰基中的任一个上与还原剂反应，然后环化，所述单酯是通过水解顺式 - 咪唑烷二羧酸二酯 式（II）其中R和Bzl各自如上定义，具有水解所述二酯中的酯基的能力的酶材料。

公开(公告)号：US4411836A

公开(公告)日：1983-10-25

申请号：US279706

申请日：1981-07-02

申请人： Naohito Ohashi ,  Shoji Nagata ,  Junki Katsube

发明人： Naohito Ohashi ,  Shoji Nagata ,  Junki Katsube

IPC分类号： C07B55/00 ,  C07B31/00 ,  C07C67/00 ,  C07C325/00 ,  C07C327/20 ,  C07C327/32 ,  C07D207/16 ,  C07C153/023

CPC分类号： C07C327/00 ,  C07D207/16

摘要： This invention relates to a process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acids of the formula [I], ##STR1## wherein R is a lower alkyl group having 1-4 carbon atoms, phenyl or substituted phenyl bearing methyl or chloro radical; a method for the racemization of an optically active .alpha.-methyl-.beta.-acylthiopropionic acid of the formula [Ia], ##STR2## wherein R is as defined above; and a process for the synthesis of captopril of the formula [II], ##STR3## using the D-acid [Ia] as an intermediate.The optically active .alpha.-methyl-.beta.-acylthiopropionic acids are useful as intermediates for the production of medicines, for example, captopril or its congeners.

摘要翻译： 本发明涉及一种用于光学拆分式[I]，其中R是具有1-4个碳原子的低级烷基的式[I]，其中R 1是苯基或 取代的含甲基或氯基的苯基; 式[Ia]的光学活性α-甲基-β-酰基硫代丙酸外消旋化的方法，其中R如上定义; 以及使用D-酸[Ia]作为中间体合成式[II]，IMAGE [II]的卡托普利的方法。