公开(公告)号：US06288056B1

公开(公告)日：2001-09-11

申请号：US09673514

申请日：2000-10-17

申请人： Atsuto Ogata ,  Norio Inomata ,  Akira Mizuno

发明人： Atsuto Ogata ,  Norio Inomata ,  Akira Mizuno

IPC分类号： A61K3155

CPC分类号： A61K31/55 ,  A61K31/496

摘要： A method of treating or improving intermittent claudication, which comprises administering, to a patient with intermittent claudication, a pyrroloazepine derivative or a pharmacologically acceptable salt thereof, said pyrroloazepine derivative being represented by the following formula (I): wherein the dotted line indicates existence or nonexistence of a bond; when the bond of the dotted line exists, X does not exist, and, when the bond of the dotted line does not exist, X represents a hydrogen atom, a hydroxy group or a group OR1 in which R1 represents a substituted or unsubstituted alkyl group; Y represents a linear or branched, substituted or unsubstituted alkyl group; Z1 and Z2 are the same or different and each independently represent a hydrogen atom, a hydroxy group or a halogen atom; and W represents a hydrogen atom or a methyl group.

摘要翻译： 一种治疗或改善间歇性跛行的方法，其包括对间歇性跛行的患者施用吡咯并氮衍生物或其药理学上可接受的盐，所述吡咯并氮衍生物由下式（I）表示：其中虚线表示存在或 不存在债券; 当存在虚线的键时，X不存在，并且当虚线的键不存在时，X表示氢原子，羟基或其中R 1表示取代或未取代的烷基的基团OR 1 ; Y表示直链或支链的取代或未取代的烷基; Z 1和Z 2相同或不同，各自独立地表示氢原子，羟基或卤素原子; W表示氢原子或甲基。

公开(公告)号：US06624314B2

公开(公告)日：2003-09-23

申请号：US09871655

申请日：2001-06-04

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Harukazu Fukami ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Harukazu Fukami ,  Norio Inomata

IPC分类号： C07D20736

CPC分类号： C07D513/04 ,  C07D207/36

摘要： A pyrrolesulfonamide derivative having the following formula (I): wherein the ring P represented by  is a pyrrole ring having the following structure: wherein R represents alkyl, cycloalkyl, cycloalkylalkyl or aralkyl; the dashed line indicates the presence or absence of a bond; l stands for 0 or 1; A represents alkylene, alkenylene or alkynylene; and Y represents a group  in which W represents CH, C═ or N; m stands for 0 or 1 when W is CH or N, or m stands for 1 when W is C═; B represents a specific divalent group; E1 and E2 each independently represents H or lower alkyl; and D represents an aromatic hydrocarbon group or heterocyclic group. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is useful as a therapeutic for circulatory diseases such as ischemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances.

摘要翻译： 具有下式（I）的吡咯磺酰胺衍生物：其中由具有以下结构的吡咯环表示的环P：其中R表示烷基，环烷基，环烷基烷基或芳烷基; 虚线表示存在或不存在键; l代表0或1; A表示亚烷基，亚烯基或亚炔基; Y表示W表示CH，C =或N的基团; 当W为CH或N时，m代表0或1，当W为C =时，m代表1; B表示特定的二价基团; E1和E2各自独立地表示H或低级烷基; D表示芳族烃基或杂环基。 化合物（I）具有强的5-羟色胺-2受体拮抗作用，毒性低，副作用小，作为循环系统疾病如缺血性心脏病，脑血管障碍和周围循环障碍的治疗有用。

公开(公告)号：US06187772B1

公开(公告)日：2001-02-13

申请号：US09147248

申请日：1998-11-12

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Norio Inomata

IPC分类号： C07D48704

CPC分类号： C07D207/416 ,  C07D487/04

摘要： Disclosed are pyrroloazepine compounds and their salts. These pyrroloazepine compounds are represented by formula (I) wherein the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2 is not present and Z1 is H but, when the bond is absent, Z1 and Z2 are both Hs; Z1 is H and Z2 is OH; Z1 and Z2 are both SR5s in which R5 is alkyl, aralkyl or aryl; or Z1 and Z2 are combined together to represent O, NOR6 in which R6 is H, alkyl, aralkyl or aryl, or C2-C3 alkylenedithio; R is H, alkyl, cycloalkyl, cycloalkyl alkyl or aralkyl; and the ring P is a specific pyrrole ring. These pyrroloazepine compounds and salts are effective as preventives or therapeutics for general circulatory diseases such as hypertension, heart failure, ischemic hear diseases, cerebrovascular disturbances and peripheral circulatory disturbances. Their production processes are also disclosed

摘要翻译： 公开了吡咯并氮化合物及其盐。 这些吡咯并氮化合物由式（I）表示，其中虚线表示存在或不存在键; 当存在键时，Z 2不存在且Z1为H，但不存在键时，Z 1和Z 2均为Hs; Z1是H，Z2是OH; Z 1和Z 2都是SR 5，其中R 5是烷基，芳烷基或芳基; 或Z 1和Z 2组合在一起以表示其中R 6为H，烷基，芳烷基或芳基或C 2 -C 3亚烷基二硫基的O，NOR 6; R为H，烷基，环烷基，环烷基烷基或芳烷基; 环P是特定的吡咯环。 这些吡咯并氮化合物和盐可用作一般循环系统疾病如高血压，心力衰竭，缺血性听觉疾病，脑血管障碍和外周循环障碍的预防剂或治疗剂。 他们的生产过程也被披露

公开(公告)号：US5962448A

公开(公告)日：1999-10-05

申请号：US875495

申请日：1997-08-21

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Tetsuo Shimamoto ,  Kyoko Nakanishi ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Tetsuo Shimamoto ,  Kyoko Nakanishi ,  Norio Inomata

IPC分类号： A61P7/00 ,  A61P9/00 ,  C07D207/34 ,  C07D487/04 ,  C07D495/20 ,  A61K31/55

CPC分类号： C07D487/04 ,  C07D207/34

摘要： A pyrroloazepine compound having the following formula (I): whereinthe ring P represented by ##STR1## is a pyrrole ring having the following structure: ##STR2## wherein R.sub.1 represents C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkyl-alkyl, C.sub.6 -C.sub.14 aryl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; and R.sub.2 represents H or C.sub.1 -C.sub.8 alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z.sub.2 is not present and Z.sub.1 represents H, but, when the bond is absent, Z.sub.1 and Z.sub.2 are both H; Z.sub.1 represents H and Z.sub.2 represents a group OR.sub.3, in which R.sub.3 represents H, C.sub.1 -C.sub.8 alkyl, or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; Z.sub.1 and Z.sub.2 both represent groups SR.sub.4, in which R.sub.4 represents C.sub.1 -C.sub.8 alkyl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; or Z.sub.1 and Z.sub.2 are combined together to represent O, a group NOR.sub.5, in which R.sub.5 represents H, or C.sub.1 -C.sub.8 alkyl or C.sub.2 -C.sub.3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C.dbd. or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C.dbd.O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E.sub.1 and E.sub.2 is H or C.sub.1 -C.sub.8 alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.

摘要翻译： PCT No.PCT / JP96 / 03522 Sec。 371日期1997年8月21日 102（e）日期1997年8月21日PCT提交1996年12月2日PCT公布。 出版物WO97 / 20845 日期：1997年6月12日具有下式（I）的吡咯并氮吡啶化合物：其中由代表的环P是具有以下结构的吡咯环：其中R1表示C1-C8烷基，C3-C8环烷基，C4-C8环烷基 - 烷基 ，任选被取代的C 6 -C 14芳基或C 7 -C 22芳烷基; 并且R 2表示H或被任选取代的C 1 -C 8烷基; 虚线表示存在或不存在键; 当存在键时，Z 2不存在，Z1表示H，但不存在键时，Z 1和Z 2均为H; Z1表示H，Z2表示OR3，其中R3表示H，任选取代的C 1 -C 8烷基或C 7 -C 22芳烷基; Z 1和Z 2均表示SR 4，其中R 4表示任选取代的C 1 -C 8烷基或C 7 -C 22芳烷基; 或Z 1和Z 2组合在一起表示O，其中R 5表示H的基团NOR 5或任选被取代的C 1 -C 8烷基或C 2 -C 3亚烷基二硫基; A表示亚烷基，亚烯基或亚炔基; 并且Y表示W为CH，C =或N的基团，m为0或1，n为1,2或3，G为O，S，C = O，亚磺酰基，磺酰基，亚烷基，亚烯基或亚磺酰基 乙缩醛 E1和E2是H或C1-C8烷基; D表示芳族烃或芳香族杂环。 化合物（I）具有强的5-羟色胺-2受体拮抗作用和低毒性和较少的副作用，并且在治疗循环系统疾病和/或与之有关的病症中是治疗上有用的。

公开(公告)号：US5874429A

公开(公告)日：1999-02-23

申请号：US669615

申请日：1996-06-24

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

IPC分类号： C07D275/06 ,  C07D279/02 ,  C07D417/06 ,  C07D513/10 ,  A61K31/54 ,  C07D279/16

CPC分类号： C07D275/06 ,  C07D279/02 ,  C07D417/06 ,  C07D513/10

摘要： Disclosed are benzothiazine derivatives represented by the following formula (I): ##STR1## The benzothiazine derivatives (I) and their salts according to the present invention have strong serotonin-2 blocking action, have excellent selectivity to this action against .alpha..sub.1 blocking action and have high safety. Accordingly, the present invention has made it possible to provide pharmaceuticals making use of antagonistic action against serotonin-2 receptors, for example, therapeutics for various circulatory diseases such as ischemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances.

摘要翻译： 公开了由下式（I）表示的苯并噻嗪衍生物：其中根据本发明的苯并噻嗪衍生物（I）及其盐具有强的5-羟色胺-2阻断作用，对α1的这种作用具有优异的选择性 阻塞作用，安全性高。 因此，本发明使得可以提供利用针对5-羟色胺-2受体的拮抗作用的药物，例如用于各种循环系统疾病如缺血性心脏病，脑血管障碍和周围循环障碍的治疗剂。

公开(公告)号：US06664251B2

公开(公告)日：2003-12-16

申请号：US09955416

申请日：2001-09-19

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

IPC分类号： C07D27916

CPC分类号： C07D275/06 ,  C07D279/02 ,  C07D417/06 ,  C07D513/10

摘要： Disclosed are benzothiazine derivatives represented by the following formula (I): wherein the dashed line indicates the presence or absence of a bond; Z represents one of the following groups: in which R1 and R2 individually represent alkyl, aralkyl or the like, R3 represents H, alkyl or the like, R4 represents H, aralkyl or the like, X1, X2 and X3 individually represent O or S, and G represents substituted or unsubstituted ethylene, trimethylene or the like; Q1 and Q2 individually represent H, OH, halogen, alkoxy or the like; A represents alkylene, alkenylene or the like; Y represents CH, C═ or N; when Y is CH, m stands for 0 or 1, n stands for 1 or 2, B represents O, S, carbonyl or the like, when Y is C═, m stands for 1, n stands for 1 or 2, B represents: in which the double bond is linked to Y, R6 represents substituted or unsubstituted aryl or the like; when Y is N, m stands for 0 or 1, n stands for 2 or 3 and B represents carbonyl, sulfonyl or the like, E1 and E2 individually represent H or lower alkyl; and D represents an aromatic hydrocarbon group or an aromatic heterocyclic group; and salts thereof. The benzothiazine derivatives (I) and their salts according to the present invention have strong serotonin-2 blocking action, have excellent selectivity to this action against &agr;1 blocking action and have high safety. Accordingly, the present invention has made it possible to provide pharmaceuticals making use of antagonistic action against serotonin-2 receptors, for example, therapeutics for various circulatory diseases such as ishemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances.

摘要翻译： 公开了由下式（I）表示的苯并噻嗪衍生物：其中虚线表示存在或不存在键; Z表示以下基团之一：其中R1和R2分别表示烷基，芳烷基等，R3表示H，烷基等，R4表示H，芳烷基等，X1，X2和X3各自表示O或S ，G表示取代或未取代的乙烯，三亚甲基等; Q1和Q2各自表示H，OH，卤素，烷氧基等; A表示亚烷基，亚烯基等; Y表示CH，C =或N; 当Y是CH时，m代表0或1，n代表1或2，B代表O，S，羰基等，当Y是C =，m代表1，n代表1或2，B代表 ：其中双键与Y连接，R​​6表示取代或未取代的芳基等; 当Y为N时，m代表0或1，n代表2或3，B代表羰基，磺酰基等，E1和E2分别代表H或低级烷基; D表示芳香族烃基或芳香族杂环基; 其盐。根据本发明的苯并噻嗪衍生物（I）及其盐具有强的5-羟色胺-2阻断作用，对该作用对α1阻断作用具有优异的选择性并具有高安全性。 因此，本发明使得可以提供利用针对5-羟色胺-2受体的拮抗作用的药物，例如用于各种循环系统疾病如血液性心脏病，脑血管障碍和外周循环障碍的治疗剂。

公开(公告)号：US06211362B1

公开(公告)日：2001-04-03

申请号：US09640010

申请日：2000-08-17

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Norio Inomata

IPC分类号： C07D48704

CPC分类号： C07D207/416 ,  C07D487/04

摘要： Disclosed are pyrroloazepine compounds and their salts. These pyrroloazepine compounds are represented by the following formula: wherein the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2 is not present and Z1 is H but, when the bond is absent, Z1 and Z2 are both Hs; Z1 is H and Z2 is OH; Z1 and Z2 are both SR5s in which R5 is alkyl, aralkyl or aryl; or Z1 and Z2 are combined together to represent O, NOR6 in which R6 is H, alkyl, aralkyl or aryl, or C2-C3 alkylenedithio; R is H, alkyl, cycloalkyl, cycloalkyl-alkyl or aralkyl; and the ring P is a specific pyrrole ring. These pyrroloazepine compounds and salts are effective as preventives or therapeutics for general circulatory diseases such as hypertension, heart failure, ischemic hear diseases, cerebrovascular disturbances and peripheral circulatory disturbances. Their production processes are also disclosed.

摘要翻译： 公开了吡咯并氮化合物及其盐。 这些吡咯并氮化合物由下式表示：其中虚线表示存在或不存在键; 当存在键时，Z 2不存在且Z1为H，但不存在键时，Z 1和Z 2均为Hs; Z1是H，Z2是OH; Z 1和Z 2都是SR 5，其中R 5是烷基，芳烷基或芳基; 或Z 1和Z 2组合在一起代表O，NOR6，其中R 6是H，烷基，芳烷基或芳基，或C 2 -C 3亚烷基二硫基; R是H，烷基，环烷基，环烷基 - 烷基或芳烷基; 环P是特定的吡咯环。 这些吡咯并氮化合物和盐可用作一般循环系统疾病如高血压，心力衰竭，缺血性听觉疾病，脑血管障碍和外周循环障碍的预防剂或治疗剂。 他们的生产过程也被披露。

公开(公告)号：US5977111A

公开(公告)日：1999-11-02

申请号：US667713

申请日：1996-06-21

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

IPC分类号： A61K31/4436 ,  A61K31/506 ,  C07D335/06 ,  C07D409/06 ,  C07D409/14 ,  C07D495/04 ,  C07D495/10 ,  C07D495/20 ,  A61K31/495

CPC分类号： C07D335/06 ,  C07D495/04 ,  C07D495/10

摘要： A thiopyran derivative represented by the following formula (I) or (I'), or the salt thereof. ##STR1## wherein A is S or --CH.dbd.CH--; the dotted line indicates that the bond may be either present or absent; Z and Z' are typically ##STR2## L is an ethylene or trimethylene group; Y is CH or N; n is 2; B is a carbonyl group; m is 0 or 1; D is a phenyl group; and E.sub.1 and E.sub.2 are hydrogen atoms. These compounds exhibit a strong serotonin-2 blocking action and highly safe. Some compounds also exhibit an .alpha..sub.1 -blocking action and therefore are useful as an antihypertensive agent with less side effects. Thus, the thiopyran derivatives are useful as drugs for the treatment of circulatory diseases in general such as hypertension, ischemic heart disease, cerebrovascular disturbance, and peripheral circulatory disturbance.

公开(公告)号：US06583296B2

公开(公告)日：2003-06-24

申请号：US09939829

申请日：2001-08-28

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Harukazu Fukami ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Kamei ,  Harukazu Fukami ,  Norio Inomata

IPC分类号： C07D20736

CPC分类号： C07D513/04 ,  C07D207/36

摘要： A pyrrolesulfonamide compound having the following formula (I): wherein the ring P represented by is a pyrrole ring having the following structure: wherein A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W represents CH, C═ or N; m stands for 0 or 1 when W is CH or N, or m stands for 1 when W is C═; B represents a specific divalent group; E1 and E2 each independently represents H or lower alkyl; and D represents an aromatic hydrocarbon group or heterocyclic group; l stands for 0 or 1; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2 is not present and Z1 represents H but, when the bond is absent, Z1 represents H and Z2 represents OH or Z1 and Z2 are combined together to represent O or a group NOR5, in which R5 represents H, or alkyl, aralkyl or aryl; and R represents H, alkyl, cycloalkyl, cycloalkyl-alkyl or aralkyl. The compound (1) has been improved in potency, selectivity to receptors other than serotonin-2 receptors, toxicity, side effects and/or the like over medicines reported to date and equipped with &agr;1-blocking action and serotonin-2 receptor antagonistic action in combination.

摘要翻译： 具有下式（I）的吡咯磺酰胺化合物：其中由具有以下结构的吡咯环表示的环P：其中A表示亚烷基，亚烯基或亚炔基; Y表示W表示CH，C =或N的基团; 当W为CH或N时，m代表0或1，当W为C =时，m代表1; B表示特定的二价基团; E1和E2各自独立地表示H或低级烷基; D表示芳族烃基或杂环基; l代表0或1; 虚线表示存在或不存在键; 当存在键时，Z 2不存在，Z1表示H，但当不存在键时，Z1表示H，Z2表示OH或Z1，Z2组合在一起表示O或NOR5基团，其中R5表示 H或烷基，芳烷基或芳基; R代表H，烷基，环烷基，环烷基 - 烷基或芳烷基。 化合物（1）对迄今为止报道的并且具有α1-阻断作用和5-羟色胺-2受体拮抗作用的药物的效力，对5-羟色胺2受体以外的受体的选择性，毒性，副作用等改善 组合。

公开(公告)号：US6100265A

公开(公告)日：2000-08-08

申请号：US353773

申请日：1999-07-15

申请人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

发明人： Akira Mizuno ,  Makoto Shibata ,  Tomoe Iwamori ,  Norio Inomata

IPC分类号： A61K31/4436 ,  A61K31/506 ,  C07D335/06 ,  C07D409/06 ,  C07D409/14 ,  C07D495/04 ,  C07D495/10 ,  C07D495/20

CPC分类号： C07D335/06 ,  C07D495/04 ,  C07D495/10

摘要： A thiopyran derivative represented by the following formula (I) or (I'), or the salt thereof. ##STR1## wherein A is S or --CH.dbd.CH--; the dotted line indicates that the bond may be either present or absent; Z and Z' are typically ##STR2## L is an ethylene or trimethylene group; Y is CH or N; n is 2; B is a carbonyl group; m is 0 or 1; D is a phenyl group; and E.sub.1 and E.sub.2 are hydrogen atoms. These compounds exhibit a strong serotonin-2 blocking action and highly safe. Some compounds also exhibit an .alpha..sub.1 -blocking action and therefore are useful as an antihypertensive agent with less side effects. Thus, the thiopyran derivatives are useful as drugs for the treatment of circulatory diseases in general such as hypertension, ischemic heart disease, cerebrovascular disturbance, and peripheral circulatory disturbance.

摘要翻译： 由下式（I）或（I'）表示的噻喃衍生物或其盐。 其中A为S或-CH = CH-; 虚线表示债券可能存在或不存在; Z和Z'通常为L是乙烯或三亚甲基; Y是CH或N; n为2; B是羰基; m为0或1; D是苯基; E1和E2是氢原子。 这些化合物表现出强烈的5-羟色胺-2阻断作用和高度安全性。 一些化合物还表现出α1-阻断作用，因此可用作具有较少副作用的抗高血压药。 因此，噻喃衍生物可用作治疗循环系统疾病的药物，例如高血压，缺血性心脏病，脑血管障碍和外周循环障碍。