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：US20050032819A1

公开(公告)日：2005-02-10

申请号：US10485865

申请日：2002-08-02

申请人： Masami Muraoka ,  Kazuki Matsui ,  Takaaki Yamamoto ,  Koji Morishita ,  Masatoshi Yuri ,  Seiji Katayama ,  Naohito Ohashi

发明人： Masami Muraoka ,  Kazuki Matsui ,  Takaaki Yamamoto ,  Koji Morishita ,  Masatoshi Yuri ,  Seiji Katayama ,  Naohito Ohashi

IPC分类号： A61P7/12 ,  A61P13/00 ,  A61P13/02 ,  C07D401/04 ,  C07D401/14 ,  A61K31/517 ,  C07D43/14

CPC分类号： C07D401/04 ,  C07D401/14

摘要： An optically active form of the quinazolinone derivatives represented by the general formula (1): [wherein Y represents a phenyl group or C2-C7 alkyl group; E represents —CH═ or nitrogen atom; and R represents a C1-C4 alkyl group and so on], or pharmaceutically acceptable salts thereof, has a selective antagonism for the M3 muscarinic receptor and depressant action on the frequency of rhythmic bladder contractions, and it is useful for the treatment of pollakiuria and urinary incontinence.

摘要翻译： 由通式（1）表示的光学活性形式的喹唑啉酮衍生物：[其中Y表示苯基或C 2 -C 7烷基; E表示-CH =或氮原子; 并且R代表C1-C4烷基等]或其药学上可接受的盐对于M3毒蕈碱受体具有选择性拮抗作用，并且对节律性膀胱收缩的频率具有抑制作用，并且可用于治疗尿频和 尿失禁

公开(公告)号：US07329665B2

公开(公告)日：2008-02-12

申请号：US10485865

申请日：2002-08-02

申请人： Masami Muraoka ,  Kazuki Matsui ,  Takaaki Yamamoto ,  Koji Morishita ,  Masatoshi Yuri ,  Seiji Katayama ,  Naohito Ohashi

发明人： Masami Muraoka ,  Kazuki Matsui ,  Takaaki Yamamoto ,  Koji Morishita ,  Masatoshi Yuri ,  Seiji Katayama ,  Naohito Ohashi

IPC分类号： A61K31/517 ,  C07D401/04 ,  C07D239/82 ,  C07D239/80

CPC分类号： C07D401/04 ,  C07D401/14

摘要： An optically active form of the quinazolinone derivatives represented by the general formula (1): [wherein Y represents a phenyl group or C2-C7 alkyl group; E represents —CH═ or nitrogen atom; and R represents a C1-C4 alkyl group and so on], or pharmaceutically acceptable salts thereof, has a selective antagonism for the M3 muscarinic receptor and depressant action on the frequency of rhythmic bladder contractions, and it is useful for the treatment of pollakiuria and urinary incontinence.

摘要翻译： 由通式（1）表示的光学活性形式的喹唑啉酮衍生物：[其中Y表示苯基或C 2 -C 7烷基; E表示-CH-或氮原子; 并且R代表C1-C4烷基等]或其药学上可接受的盐对于M3毒蕈碱受体具有选择性拮抗作用，并且对节律性膀胱收缩的频率具有抑制作用，并且可用于治疗尿频和 尿失禁

公开(公告)号：US06645971B1

公开(公告)日：2003-11-11

申请号：US09807173

申请日：2001-04-10

申请人： Masami Muraoka ,  Kazuki Matsui ,  Koji Morishita ,  Naohito Ohashi

发明人： Masami Muraoka ,  Kazuki Matsui ,  Koji Morishita ,  Naohito Ohashi

IPC分类号： A61K31517

CPC分类号： C07D401/04

摘要： A compound given by general formula (1): [wherein T represents oxygen or sulfur atom, Y represents alkyl, cycloalkyl group, etc., ring W represents benzene ring, etc., R1 and R2 represent independently hydrogen atom, lower alkyl group, etc., and R3 represents hydrogen atom, alkyl group, etc. Z represents a group given by formula: {wherein A1 and A2 represent independently hydrogen atom, alkyl group, etc. and G represents straight chain alkylene having 1-6 of the carbon number, etc.} or a group given by formula: {wherein n represents 0, 1 or 2, ring E represents 4-8 membered saturated heterocyclic ring containing nitrogen atom(s), and A3 represents hydrogen atom, alkyl group, etc.}], its prodrug or pharmaceutically acceptable salt thereof is an antagonist against muscarinic receptor that is useful as anticholinergic medicaments, and therefore it is useful as pollakiuria or urinary incontinence remedy.

摘要翻译： 由通式（1）表示的化合物：[其中T表示氧或硫原子，Y表示烷基，环烷基等，环W表示苯环等，R 1和R 2独立地表示氢 原子，低级烷基等，R 3表示氢原子，烷基等。Z表示由下式给出的基团：其中A 1和A 2独立地表示氢原子，烷基， G表示具有1-6个碳数的直链亚烷基等}或由式表示的基团：其中n表示0,1或2，环E表示含有氮原子的4-8元饱和杂环 并且A 3表示氢原子，烷基等}，其前药或其药学上可接受的盐是可用作抗胆碱能药物的毒蕈碱受体拮抗剂，因此可用作尿频或尿 失禁补救

公开(公告)号：US4544635A

公开(公告)日：1985-10-01

申请号：US579602

申请日：1984-02-13

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

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.

公开(公告)号：US4325886A

公开(公告)日：1982-04-20

申请号：US209680

申请日：1980-11-24

申请人： Naohito Ohashi ,  Hiroyuki Mizote ,  Isamu Maruyama ,  Shoji Nagata ,  Kikuo Ishizumi ,  Junki Katsube

发明人： Naohito Ohashi ,  Hiroyuki Mizote ,  Isamu Maruyama ,  Shoji Nagata ,  Kikuo Ishizumi ,  Junki Katsube

IPC分类号： C07C319/28 ,  C07C67/00 ,  C07C313/00 ,  C07C323/52 ,  C07C325/00 ,  C07C327/20 ,  C07C327/32 ,  C07C153/07 ,  C07C153/09

CPC分类号： C07C327/00

摘要： A process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acid, which comprises contacting a DL-.alpha.-methyl-.beta.-acylthiopropionic acid of the formula, ##STR1## wherein R.sub.1 is acetyl or benzoyl which may be substituted with a C.sub.1 -C.sub.3 alkyl or a halogen atom, with an optically active amine of the formula, ##STR2## wherein R.sub.2 is methyl, isopropyl or isobutyl, to form diastereoisomeric salts, subjecting the formed diastereoisomeric salts to the fractional crystallization in a solvent to separate the D-acid salt from the L-acid salt, and then contacting the individual diastereoisomeric salt with acid to give D-.alpha.-methyl-.beta.-acylthiopropionic acid and L-.alpha.-methyl-.beta.-acylthiopropionic acid, the former being useful as an intermediate for synthesizing captopril useful as an antihypertensive agent.

摘要翻译： 用于DL-α-甲基-β-酰基硫代丙酸的光学拆分的方法，其包括使下式的DL-α-甲基-β-酰基硫代丙酸：其中R 1是乙酰基或可以被 C 1 -C 3烷基或卤素原子，与下式的光学活性胺，其中R 2是甲基，异丙基或异丁基，形成非对映异构盐，使形成的非对映异构体盐在溶剂中进行分级结晶以分离 来自L-酸盐的D-酸盐，然后将各个非对映异构体盐与酸接触，得到D-α-甲基-β-酰基硫代丙酸和L-α-甲基-β-酰基硫代丙酸，前者可用作 用作合成用作抗高血压药的卡托普利的中间体。

公开(公告)号：US06248772B1

公开(公告)日：2001-06-19

申请号：US09604826

申请日：2000-06-27

申请人： Masahumi Kitano ,  Kazuhiro Nakano ,  Hideki Yagi ,  Naohito Ohashi ,  Atsuyuki Kojima ,  Tsuyoshi Noguchi ,  Akira Miyagishi

发明人： Masahumi Kitano ,  Kazuhiro Nakano ,  Hideki Yagi ,  Naohito Ohashi ,  Atsuyuki Kojima ,  Tsuyoshi Noguchi ,  Akira Miyagishi

IPC分类号： A61K31404

CPC分类号： C07D209/08 ,  C07D209/42

摘要： Novel indoloylguanidine derivatives shown by formula (1), wherein R1 represents one or more, the same or different substituent(s) which is selected from the group consisting of a hydrogen atom, an alkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a halogen atom, nitro group, an acyl group, carboxyl group, an alkoxycarbonyl group, an aromatic group, and a group shown by formula: —OR3, —NR6R7, —SO2NR6R7 or —S(O)nR40; and R2 represents a hydrogen atom, an alkyl group, a substituted alkyl group, a cycloalkyl group, hydroxy group, an alkoxy group or a group shown by formula: —CH2R20; and which inhibit the Na+/H+ exchanger activity and are useful for the treatment and prevention of a disease caused by increased Na+/H+ exchanger activity, such as hypertension, arrhythmia, angina pectoris, cardiac hypertrophy, diabetes, disorders associated with ischemia or ischemic reperfusion, cerebro-ischemic disorders; or diseases caused by excessive cell proliferation.

公开(公告)号：US4297282A

公开(公告)日：1981-10-27

申请号：US90857

申请日：1979-11-02

申请人： Naohito Ohashi ,  Shoji Nagata ,  Junki Katsube

发明人： Naohito Ohashi ,  Shoji Nagata ,  Junki Katsube

IPC分类号： C07C327/00 ,  C07D207/16 ,  C07C153/017

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。 光学活性α-甲基-β-酰基硫代丙酸可用作生产药物的中间体，例如卡托普利或其同系物。

公开(公告)号：US06369110B1

公开(公告)日：2002-04-09

申请号：US09701269

申请日：2000-11-27

申请人： Masahumi Kitano ,  Naohito Ohashi

发明人： Masahumi Kitano ,  Naohito Ohashi

IPC分类号： C07C27902

CPC分类号： C07D223/16 ,  C07C279/22 ,  C07C317/44 ,  C07C323/62 ,  C07C2602/10 ,  C07C2602/12 ,  C07D215/54 ,  C07D225/06

摘要： A compound represented by the general formula (1): wherein each of R1, R2, R3, R4 and R5 is a hydrogen atom, an alkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a saturated heterocyclic group, an aromatic group, an acyl group or the like; each of Y1, Y2, Y3 and Y4 is a single bond, —CH2—, —O—, —CO— or the like, provided that at least two of Y1 through Y4 are independently a group other than a single bond; and Z may be absent, or one or more Zs may be present and are independently an alkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a saturated heterocyclic group, a halogen atom, a carboxyl group, an alkoxycarbonyl group, an aromatic group, an acyl group or the like, is useful as a therapeutic or prophylactic agent for diseases caused by the acceleration of the sodium/proton exchange transport system.

摘要翻译： 由通式（1）表示的化合物：其中R 1，R 2，R 3，R 4和R 5各自为氢原子，烷基，取代的烷基，烯基，炔基，环烷基， 环烯基，饱和杂环基，芳基，酰基等; Y 1，Y 2，Y 3和Y 4中的每一个为单键，-CH 2 - ， - O - ， - CO-等，条件是Y 1至Y 4中的至少两个独立地为除单键以外的基团。 Z可以不存在，也可以是一个以上的Z，可以独立地为烷基，取代的烷基，烯基，炔基，环烷基，环烯基，饱和杂环基，卤素原子， 羧基，烷氧基羰基，芳香族基，酰基等可用作由加速钠/质子交换系统引起的疾病的治疗或预防剂。

公开(公告)号：US06271251B1

公开(公告)日：2001-08-07

申请号：US09342101

申请日：1999-06-29

申请人： Masahumi Kitano ,  Naohito Ohashi

发明人： Masahumi Kitano ,  Naohito Ohashi

IPC分类号： A61K3140

CPC分类号： C07D471/06 ,  C07D487/06

摘要： A substituted guanidine derivative represented by the general formula: or a pharmaceutically acceptable acid addition salt thereof, is useful as a therapeutic or prophylactic agent for diseases caused by the acceleration of the sodium/proton (Na+/H+) exchange transport system, for example, hyperpiesia, arrhythmia, angina pectoris, hypercardia, diabetes, organopathies due to ischemia or ischemia re-perfusion, troubles due to cerebral ischemia, diseases caused by cell over-proliferations, and diseases caused by trouble with endothelial cells.

摘要翻译： 由通式表示的取代的胍衍生物或其药学上可接受的酸加成盐可用作由加速钠/质子（Na + / H +）交换转运系统引起的疾病的治疗或预防剂，例如， 高血压，心律失常，心绞痛，高血压，糖尿病，由于局部缺血或缺血再灌注引起的有机病变，由于脑缺血引起的麻烦，由细胞过度增殖引起的疾病以及由内皮细胞引起的疾病引起的疾病。