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：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：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：US07057036B2

公开(公告)日：2006-06-06

申请号：US10615836

申请日：2003-07-10

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： C07D267/02 ,  C07D513/00 ,  C07D207/00

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, cycloalkyl-alkyl or aralkyl; 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 NOR1, in which R1 represents H, or alkyl, aralkyl or aryl; 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：其中由代表的环P是具有以下结构的吡咯环：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; 并且当存在键时，Z 2不存在，Z 1表示H，但当该键不存在时，Z 1表示 H和Z 2代表OH或Z 1和Z 2 2组合在一起，表示O或NOR 1或N 2 其中R 1表示H，或烷基，芳烷基或芳基; 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; E 1和E 2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：US06743913B2

公开(公告)日：2004-06-01

申请号：US10421929

申请日：2003-04-24

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： C07D51304

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：US06331623B1

公开(公告)日：2001-12-18

申请号：US09367842

申请日：1999-08-26

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： C07O51334

CPC分类号： C07D513/04 ,  C07D207/36

摘要： A pyrrolesulfonamide compound having formula (I) wherein the ring P represented by &agr; is a pyrrole ring having structure &bgr; or &psgr; wherein A represents alkylene, alkenylene or alkynylene; and Y represents a group &dgr; 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 a &agr;1-blocking action and serotonin-2 receptor antagonistic action in combination.

摘要翻译： 具有式（I）的吡咯磺酰胺化合物，其中由α表示的环P是具有β或psi结构的吡咯环，其中A表示亚烷基，亚烯基或亚炔基; 并且Y表示其中W表示CH，C =或N的组δ; 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）对于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，对5-羟色胺-2受体以外的受体的效力，选择性，毒性，副作用等改善， 结合。

公开(公告)号：US06271223B1

公开(公告)日：2001-08-07

申请号：US09367841

申请日：1999-08-26

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： A61K3155

CPC分类号： C07D513/04 ,  C07D207/36

摘要： A pyrrolesulfonamide derivative having the following formula (I): is provided wherein P, A, Y, l, Z1 and Z2 are as described herein, wherein the derivative has strong serotonin-2 receptor antagonistic action, low toxicity and fewer side effects, and its use as a therapeutic for circulatory diseases such as ischemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances.

摘要翻译： 提供具有下式（I）的吡咯磺酰胺衍生物：其中P，A，Y，l，Z 1和Z 2如本文所述，其中衍生物具有强的5-羟色胺-2受体拮抗作用，低毒性和较少的副作用， 其用作循环系统疾病如缺血性心脏病，脑血管障碍和外周循环障碍的治疗剂。

公开(公告)号：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。