公开(公告)号：US4851413A

公开(公告)日：1989-07-25

申请号：US4138

申请日：1987-01-16

申请人： Shinji Terao ,  Kohei Nishikawa

发明人： Shinji Terao ,  Kohei Nishikawa

IPC分类号： A61K31/445 ,  A61K31/33 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/425 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4433 ,  A61P3/06 ,  A61P9/00 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P25/28 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07C50/02 ,  C07D213/16 ,  C07D213/50 ,  C07D213/55 ,  C07D213/56 ,  C07D233/40 ,  C07D233/60 ,  C07D233/61 ,  C07D233/64 ,  C07D277/22 ,  C07D409/06 ,  C07D521/00 ,  C12N9/99

CPC分类号： C07D231/12 ,  C07D213/50 ,  C07D213/55 ,  C07D233/56 ,  C07D249/08 ,  C07D409/06

摘要： Quinone derivatives represented by the general formula ##STR1## (wherein, R.sup.1 and R.sup.2, the same or different, refer to a hydrogen atom, methyl or methoxymethyl group, or R.sup.1 and R.sup.2 bind together to form --CH.dbd.CH--CH.dbd.CH--; R.sup.3 is a hydrogen atom or methyl group; R.sup.4 is a nitrogen-containing heterocyclic group which may be substituted; R.sup.5 is a hydrogen atom, methyl group, hydroxymethyl group which may be substituted, or a carboxyl group which may be esterified or amidated; Z is ##STR2## (wherein, R' is hydrogen atom or methyl group); n is an integer from 0 through 12, m is an integer from 0 through 3, and k is an integer from 0 through 7, providing that, when m is 2 or 3, Z and k are able to vary appropriately in the repeating unit shown in [ ]), and the hydroquinone derivatives thereof, are novel compounds, possess improvement effects of metabolism of polyunsaturated fatty acids, particularly two or more of inhibition of production of fatty acid peroxides, inhibition of production of metabolites in 5-lipoxygenase pathway, inhibition of thromboxane A.sub.2 synthetase, thromboxane A.sub.2 receptor antagonism and scavenging action of active oxygen species, and of use as drugs, such as antithrombotics, anti-vascular constriction agents, anti-asthma agent, antiallergic agents, therapeutics for psoriasis, agents for improvement in heart, brain and cardiovascular systems, therapeutics for nephritis, active oxygen-eliminating agents, anticancer agents, agents for improvement of control of arachidonate cascade products, etc.

摘要翻译： 由通式（I）表示的喹喔啉衍生物（其中，R 1和R 2相同或不同，指氢原子，甲基或甲氧基甲基，或R 1和R 2结合在一起形成-CH = CH-CH = CH-; R3是氢原子或甲基; R4是可以被取代的含氮杂环基; R5是氢原子，甲基，可以被取代的羟甲基或可被酯化的羧基 或酰胺化; Z为 + TR （其中，R'为氢原子或甲基）; n为0〜12的整数，m为0〜3的整数，k为 0至7，条件是当m为2或3时，Z和k能够以[]）所示的重复单元适当变化，其氢醌衍生物为新型化合物，具有改善多不饱和脂肪酸代谢的效果 酸，特别是两种或更多种抑制脂肪酸过氧化物的产生，抑制生产 的5-脂氧合酶途径中的代谢物，血栓烷A2合成酶的抑制，血栓素A2受体拮抗作用和活性氧的清除作用，以及用作药物如抗血栓形成剂，抗血管收缩剂，抗哮喘剂，抗过敏剂， 银屑病治疗剂，心脏，脑和心血管系统改善剂，肾炎治疗剂，活性氧消除剂，抗癌剂，改善花生四烯酸级联产物的控制剂等。

公开(公告)号：US4727078A

公开(公告)日：1988-02-23

申请号：US502603

申请日：1983-06-09

申请人： Shinji Terao ,  Kohei Nishikawa

发明人： Shinji Terao ,  Kohei Nishikawa

IPC分类号： C07C51/363 ,  C07D201/08 ,  C07D213/26 ,  C07D213/30 ,  C07D213/32 ,  C07D213/50 ,  C07D213/55 ,  C07D213/57 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07F9/54

CPC分类号： C07D213/30 ,  C07C51/363 ,  C07D201/08 ,  C07D213/26 ,  C07D213/32 ,  C07D213/50 ,  C07D213/55 ,  C07D213/57 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07F9/5407

摘要： Novel compound of the formula: ##STR1## wherein R.sup.1 is pyridyl group, R.sup.2 is a phenyl group, a thienyl group, a furyl group, a naphthyl group, a benzothienyl group or pyridyl group, which may optionally have a lower alkoxy group, a lower alkyl group, a halogen atom, trifluoromethyl group, a lower alkenyl group or methylenedioxy group, R.sup.3 is hydrogen atom or a lower alkyl group, and n is an integer of 0 to 6, Y is sulphur atom, methylene group or a group of the formula: ##STR2## wherein R.sup.4 is hydrogen atom or acetyl group, and m is 0 or 1, and their pharmaceutically acceptable salts have an inhibitory action on bio-synthesis of thromboxane A.sub.2 (TXA.sub.2) and an effect of accelerating the productivility of prostaglandin I.sub.2 (PGI.sub.2), and can be used for mammals to the prophylaxis or therapy of thrombosis caused by platelet aggregation or ischemic diseases caused by vasospasms in cardiac, cerebral and peripheral circulatory system (e.g. cardiac infarction, apoplexy, infarct of blood vessels in kidney, lung and other organs, pectic ulcer, etc.).

摘要翻译： 下式的新型化合物：其中R 1为吡啶基，R 2为可任选具有低级烷氧基的苯基，噻吩基，呋喃基，萘基，苯并噻吩基或吡啶基， 低级烷基，卤原子，三氟甲基，低级烯基或亚甲二氧基，R3为氢原子或低级烷基，n为0〜6的整数，Y为硫原子，亚甲基或 其中R4为氢原子或乙酰基，m为0或1，其药学上可接受的盐对凝血恶烷A2（TXA2）的生物合成具有抑制作用，并且增加前列腺素的生产性的作用 I2（PGI2），可用于哺乳动物预防或治疗由心脏，脑和周围循环系统（例如心脏梗塞，中风，肾脏血管梗死）引起的血小板聚集或血管痉挛引起的血栓形成， 肺等器官，果胶性溃疡等）。

公开(公告)号：US4640916A

公开(公告)日：1987-02-03

申请号：US803217

申请日：1985-11-27

申请人： Kanji Meguro ,  Kohei Nishikawa

发明人： Kanji Meguro ,  Kohei Nishikawa

IPC分类号： C07D279/14 ,  C07D279/16 ,  C07D513/04 ,  C07D417/06 ,  A61K31/54

CPC分类号： C07D513/04 ,  C07D279/14 ,  C07D279/16

摘要： 1,4-Benzothiazine derivatives of the formula; ##STR1## wherein R.sup.1 and R.sup.2 independently stand for hydrogen, halogen, a lower alkyl group, a lower alkoxy group or trifluoromethyl group, or R.sup.1 and R.sup.2, taken together, form a 5-7 membered ring represented by ##STR2## wherein n is an integer of 3 to 5 or a 5-6 membered ring represented by ##STR3## wherein m is 1 or 2, R.sup.3 and R.sup.4 independently stand for hydrogen, halogen, a lower alkyl group, a lower alkoxy group or trifluoromethyl group, R.sup.5 stands for hydrogen or a lower alkyl group, and A stands for an alkylene group or pharmaceutically acceptable salts thereof, are useful as prophylactic or therapeutic drugs for, among others, hypertension and ischemic cardiovascular diseases.

摘要翻译： 式的1,4-苯并噻嗪衍生物; 其中R 1和R 2独立地代表氢，卤素，低级烷基，低级烷氧基或三氟甲基，或者R 1和R 2一起形成由表示的5-7元环，其中n是 3〜5的整数或由下式表示的5-6元环，其中m为1或2，R3和R4分别代表氢，卤素，低级烷基，低级烷氧基或三氟甲基，R5代表 对于氢或低级烷基，A表示亚烷基或其药学上可接受的盐，可用作高血压和缺血性心血管疾病等预防或治疗药物。

公开(公告)号：US4638000A

公开(公告)日：1987-01-20

申请号：US691005

申请日：1985-01-14

申请人： Hirosada Sugihara ,  Kohei Nishikawa ,  Katsumi Ito

发明人： Hirosada Sugihara ,  Kohei Nishikawa ,  Katsumi Ito

IPC分类号： A61K38/00 ,  C07D209/48 ,  C07D211/22 ,  C07D211/34 ,  C07D213/55 ,  C07D267/14 ,  C07D281/10 ,  C07D309/08 ,  C07D335/02 ,  C07D417/04 ,  C07K5/02 ,  A61K31/55 ,  C07D417/12

CPC分类号： C07D209/48 ,  C07D211/22 ,  C07D211/34 ,  C07D213/55 ,  C07D267/14 ,  C07D281/10 ,  C07D309/08 ,  C07D335/02 ,  C07D417/04 ,  C07K5/0222 ,  A61K38/00

摘要： Novel condensed seven-membered ring compounds of the formula: ##STR1## [wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, or both jointly form tri- or tetramethylene; R.sup.3 and R.sup.5 are independently hydrogen, lower alkyl or aralkyl; R.sup.4 is hydrogen or lower alkyl; R.sup.6 is a condensed or non-condensed hetero-alicyclic containing at least one atom of N, O and S as a ring-forming atom which may be substituted; A is an alkylene chain; n is 1 or 2] and salts thereof.These compounds exhibit inhibitory activity on angiotensin converting enzyme and so forth, and are of value as an agent for diagnosis, prevention and treatment of circulatory diseases, such as hypertension, cardiopathy and cerebral apoploxy.

摘要翻译： 新颖的具有下式的稠合的七元环化合物：其中R 1和R 2独立地是氢，卤素，三氟甲基，低级烷基或低级烷氧基，或两者共同形成三 - 或四亚甲基; R3和R5独立地是氢，低级烷基或芳烷基; R4是氢或低级烷基; R6是含有至少一个N，O和S原子的缩合或非稠合的杂脂环，其可以被取代成环原子; A是亚烷基链; n为1或2]及其盐。 这些化合物对血管紧张素转换酶等表现出抑制活性，作为诊断，预防和治疗循环系统疾病如高血压，心脏病和脑酰胞磷脂的药物具有价值。

公开(公告)号：US4472383A

公开(公告)日：1984-09-18

申请号：US485824

申请日：1983-04-18

申请人： Yoshikazu Oka ,  Kohei Nishikawa

发明人： Yoshikazu Oka ,  Kohei Nishikawa

IPC分类号： C07K5/08 ,  A61K38/55 ,  A61P9/12 ,  A61P43/00 ,  C07K1/113 ,  C07K5/02 ,  C07K14/81 ,  C12N9/99 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K5/022

摘要： Novel peptide derivatives, inclusive of salts thereof, of the formula ##STR1## wherein A represents monocyclic or bicyclic hydrocarbon group, R.sup.1 and R.sup.3 are independently hydrogen, C.sub.1-4 alkyl or phenyl-C.sub.1-4 alkyl, and R.sup.2, R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-4 alkyl, have inhibitory activities of angiotensin converting enzyme and bradykinin decomposing enzyme, and are useful as antihypertensive agents.

摘要翻译： 其中A表示单环或双环烃基，R1和R3独立地是氢，C1-4烷基或苯基-C1-4烷基，R2，R4和R5是新的肽衍生物，包括其盐， 独立氢或C 1-4烷基具有血管紧张素转换酶和缓激肽分解酶的抑制活性，可用作抗高血压药。

公开(公告)号：US4340598A

公开(公告)日：1982-07-20

申请号：US204356

申请日：1980-11-05

申请人： Yoshiyasu Furukawa ,  Shoji Kishimoto ,  Kohei Nishikawa

发明人： Yoshiyasu Furukawa ,  Shoji Kishimoto ,  Kohei Nishikawa

IPC分类号： A61K31/415 ,  A61P9/12 ,  C07D233/54 ,  C07D233/64 ,  C07D233/68 ,  C07D233/90

CPC分类号： C07D233/64 ,  C07D233/90

摘要： Novel imidazole derivatives of the formula: ##STR1## wherein R.sup.1 is lower alkyl or, phenyl-C.sub.1-2 alkyl which may be substituted with halogen or nitro;R.sup.2 is lower alkyl, cycloalkyl or, phenyl which may be substituted with halogen, lower alkyl, lower alkoxyl or di(lower alkyl)amino,one of R.sup.3 and R.sup.4 is of the formula: --(CH.sub.2).sub.n --COR.sup.5 in the formula R.sup.5 is amino, lower alkoxyl or hydroxyl and n is integer of 0, 1 or 2,and the other is hydrogen or halogen;provided that R.sup.1 is lower alkyl or phenethyl when R.sup.3 is halogen, n is 1 and R.sup.5 is lower alkoxyl or hydroxyl, and their salts have hypotensive activity.

摘要翻译： 下式的新型咪唑衍生物：其中R 1是低级烷基或被卤素或硝基取代的苯基-C 1-2烷基; R 2是低级烷基，环烷基或可被卤素，低级烷基，低级烷氧基或二（低级烷基）氨基取代的苯基，R 3和R 4中的一个具有下式： - （CH 2）n COR 5在式R 5 是氨基，低级烷氧基或羟基，n是0,1或2的整数，另一个是氢或卤素; 条件是当R 3为卤素时，R 1为低级烷基或苯乙基，n为1，R 5为低级烷氧基或羟基，并且它们的盐具有降血压活性。

公开(公告)号：US20070259932A1

公开(公告)日：2007-11-08

申请号：US11594982

申请日：2006-11-09

申请人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

发明人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

IPC分类号： A61K31/4184 ,  A61K31/41 ,  A61P13/12 ,  A61P9/04 ,  A61P9/12 ,  C07D257/04 ,  C07D403/10

CPC分类号： C07D235/02 ,  C07D235/26 ,  C07D235/28 ,  C07D235/30 ,  C07D403/04 ,  C07D403/10 ,  C07D405/14

摘要： Benzimidazole derivatives of the formula (I): wherein the ring A is a benzene ring which may optionally contain substitution in addition to the R′ group; R1 is hydrogen or an optionally substituted hydrocarbon residue; R2 is a group capable of forming an anion or a group convertible thereinto; X is a direct bond or a spacer having an atomic length of two or less between the phenylene group and the phenyl group; R′ is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or convertible to an anion; Y is —O—, —S(O)m— or —N(R4)— wherein m is an integer of 0, 1 or 2 and R4 is hydrogen or an optionally substituted alkyl group; and n is an integer of 1 or 2; and the pharmaceutically acceptable salts thereof, have potent angiotensin II antagonistic activity and antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.

摘要翻译： 式（I）的苯并咪唑衍生物：其中环A是可以任选地除R'基团之外的取代基的苯环; R 1是氢或任选取代的烃残基; R 2是能够形成阴离子或可转换的基团的基团; X是亚苯基和苯基之间的原子长度为2以下的直接键或间隔物; R'是羧基，其酯，其酰胺或能够形成阴离子或可转化成阴离子的基团; Y是-O - ， - S（O）m - 或-N（R 4） - ，其中m是0,1或2的整数，R 0 > 4是氢或任选取代的烷基; n为1或2的整数; 和其药学上可接受的盐具有有效的血管紧张素II拮抗活性和抗高血压活性，因此可用作治疗循环系统疾病如高血压疾病，心脏病（例如高血压，心力衰竭，心肌梗塞等），中风 ，脑中风，肾炎等

公开(公告)号：US06844443B2

公开(公告)日：2005-01-18

申请号：US10612984

申请日：2003-07-07

申请人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

发明人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

IPC分类号： A61P9/12 ,  C07D235/02 ,  C07D235/26 ,  C07D235/28 ,  C07D235/30 ,  C07D403/10 ,  C07D257/04

CPC分类号： C07D235/02 ,  C07D235/26 ,  C07D235/28 ,  C07D235/30 ,  C07D403/04 ,  C07D403/10 ,  C07D405/14

摘要： A method for producing a compound represented by the formula: wherein the ring A is a benzene ring which may be substituted in addition to the R′ group; R1 is hydrogen or an optionally substituted hydrocarbon residue; X is a direct bond or a spacer having an atomic length or two or less between the phenylene group and the phenyl group; Y is —O—, —S(O)m- or —N(R4)— wherein m is an integer of 0, 1 or 2 and R4 is hydrogen or an optionally substituted alkyl group; R′ is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or a group convertible thereinto; n is an integer of 1 or 2; or a salt thereof, which comprises deprotecting a compound represented by the formula: wherein R is triphenylmethyl, 2-tetrahydropyranyl, methoxymethyl or ethoxy methyl, the other symbols as defined above; or a salt thereof.

摘要翻译： 一种制备由下式表示的化合物的方法：其中环A是除R'基之外可被取代的苯环; R 1是氢或任选取代的烃残基; X是在亚苯基和苯基之间具有原子长度或者两个或更少的直接键或间隔子; Y是-O - ， - S（O）m - 或-N（R 4） - ，其中m是0,1或2的整数，R 4是氢或任选取代的烷基; R'是羧基，其酯，其酰胺或能够形成阴离子的基团或可转化的基团; n为1或2的整数; 其包括使由下式表示的化合物脱保护：其中R是三苯甲基，2-四氢吡喃基，甲氧基甲基或乙氧基甲基，其它符号如上定义; 或其盐。

公开(公告)号：US5889036A

公开(公告)日：1999-03-30

申请号：US965416

申请日：1997-11-06

申请人： Kohei Nishikawa ,  Yumiko Shibouta ,  Keiji Kubo

发明人： Kohei Nishikawa ,  Yumiko Shibouta ,  Keiji Kubo

IPC分类号： A61K31/415 ,  A61K31/4184 ,  A61K31/4245 ,  A61P3/08 ,  A61P3/10 ,  A61P13/02 ,  A61P15/00 ,  A61P29/00 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  A61K31/41

CPC分类号： A61K31/4184 ,  A61K31/415 ,  A61K31/4245

摘要： This invention relates to prophylactic or therapeutic drug for diabetic nephropathy or glomerulonephritis, comprising, as an active ingredient, a compound or salt thereof represented by general formula (I) ##STR1## wherein R.sup.1 stands for H or an optionally substituted hydrocarbon residue; R.sup.2 stands for an optionally esterified carboxyl group; R.sup.3 stands for a group actually or potentially capable of forming an anion; X shows that the phenylene and phenyl groups bind to each other directly or through a spacer having an atomic chain length of two or less; n stands for 1 or 2; ring A stands for a benzene ring having an optional substituent in addition to R.sup.2 ; Y stands for a bond, --O--, --S(O).sub.m -- (wherein m stands for 0, 1 or 2), or --N(R.sup.4)-- (wherein R.sup.4 stands for H or an optionally substituted alkyl group).

摘要翻译： 本发明涉及用于糖尿病性肾病或肾小球肾炎的预防或治疗药物，其包含作为活性成分的由通式（I）表示的化合物或其盐，其中R1代表H或任选取代的烃残基 ; R2代表任选酯化的羧基; R3代表实际上或潜在能够形成阴离子的组; X表示亚苯基和苯基直接或通过原子链长度为2或更小的间隔物彼此结合; n代表1或2; 环A代表除R2之外具有任选取代基的苯环; Y代表键，-O - ， - S（O）m-（其中m代表0,1或2）或-N（R 4） - （其中R 4表示H或任选取代的烷基）。

公开(公告)号：US5703110A

公开(公告)日：1997-12-30

申请号：US715100

申请日：1996-09-17

申请人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

发明人： Takehiko Naka ,  Kohei Nishikawa ,  Takeshi Kato

IPC分类号： C07D235/02 ,  C07D235/26 ,  C07D235/28 ,  C07D235/30 ,  C07D403/10 ,  A01N43/50 ,  A61K31/41 ,  C07D235/12

CPC分类号： C07D235/02 ,  C07D235/26 ,  C07D235/28 ,  C07D235/30 ,  C07D403/10

摘要： Benzimidazole derivatives of the formula (I): ##STR1## wherein the ring A is a benzene ring which may optionally contain substitution in addition to the R' group; R.sup.1 is hydrogen or an optionally substituted hydrocarbon residue; R.sup.2 is a group capable of forming an anion or a group convertible thereinto; X is a direct bond or a spacer having an atomic length of two or less between the phenylene group and the phenyl group; R' is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or convertible to an anion; Y is --O--, --S(O).sub.m -- or --N(R.sup.4)-- wherein m is an integer of 0, 1 or 2 and R.sup.4 is hydrogen or an optionally substituted alkyl group; and n is an integer of 1 or 2; and the pharmaceutically acceptable salts thereof, have potent angiotensin II antagonistic activity and antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.

摘要翻译： 式（I）的苯并咪唑衍生物：其中环A是可以任选地含有取代基的R'基团的苯环; R1是氢或任选取代的烃残基; R2是能够形成阴离子或可转换的基团的基团; X是亚苯基和苯基之间的原子长度为2以下的直接键或间隔物; R'是羧基，其酯，其酰胺或能够形成阴离子或可转化成阴离子的基团; Y是-O - ， - S（O）m - 或-N（R4） - ，其中m是0,1或2的整数，R4是氢或任选取代的烷基; n为1或2的整数; 和其药学上可接受的盐具有有效的血管紧张素II拮抗活性和抗高血压活性，因此可用作治疗循环系统疾病如高血压疾病，心脏病（例如高血压，心力衰竭，心肌梗塞等），中风 ，脑中风，肾炎等