公开(公告)号：US5399557A

公开(公告)日：1995-03-21

申请号：US30427

申请日：1993-04-07

申请人： Akira Mizuno ,  Mikiko Miya ,  Norio Inomata ,  Toshio Tatsuoka ,  Takafumi Ishihara

发明人： Akira Mizuno ,  Mikiko Miya ,  Norio Inomata ,  Toshio Tatsuoka ,  Takafumi Ishihara

IPC分类号： C07D487/04 ,  A61K31/55

CPC分类号： C07D487/04

摘要： This invention provides a pyrroloazepine compound represented by the following formula (I) or (II): ##STR1## wherein Z.sub.1, Z.sub.2, R, A and Y are defined in the claims. The pyrroloazepine compounds according to the present invention are drugs having excellent anti-serotonin action. Coupled with their high safety, they can therefore be used as novel therapeutics for ischemic heart diseases. In addition, the compounds of the present invention include those having anti-.alpha..sub.1 action. Such compounds are effective as hypotensive drugs. Pyrroloazepine compounds according to the present invention are therefore extremely useful as therapeutics for a wide variety of circulatory diseases.

摘要翻译： PCT No.PCT / JP92 / 01009 Sec。 371日期：1993年4月7日 102（e）日期1993年4月7日PCT提交1992年8月6日PCT公布。 公开号WO93 / 03032 日本特开昭通1 9 9 3年2月18日。本发明提供由下式（I）或（II）表示的吡咯并氮杂化合物：其中Z1，Z2，R，A和Y定义 在权利要求中。 根据本发明的吡咯并氮吡啶化合物是具有优异的抗5-羟色胺作用的药物。 结合高安全性，因此可用作缺血性心脏病的新疗法。 此外，本发明的化合物包括具有抗α1作用的化合物。 这些化合物作为降压药有效。 因此，根据本发明的吡罗洛西泮化合物作为多种循环系统疾病的治疗剂非常有用。

公开(公告)号：US06713634B2

公开(公告)日：2004-03-30

申请号：US10188234

申请日：2002-07-03

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： C07D20700

CPC分类号： C07D487/04 ,  C07D207/34

摘要： A method of effecting serotonin-2-receptor antagonism in a mammal in need thereof, which includes administering to the mammal an effective amount of the compound of the formula (I), or a pharmaceutically acceptable salt thereof: wherein ring P, the dashed line, A, Y, Z1 and Z2 are defined herein.

摘要翻译： 一种在有需要的哺乳动物中实现5-羟色胺-2-受体拮抗作用的方法，其包括向哺乳动物施用有效量的式（I）化合物或其药学上可接受的盐：其中环P为虚线 A，Y，Z 1和Z 2在本文中定义。

公开(公告)号：US06316442B1

公开(公告)日：2001-11-13

申请号：US09379853

申请日：1999-08-24

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： A61K3154

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.

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亚乙基，三亚甲基等。

公开(公告)号：US06258805B1

公开(公告)日：2001-07-10

申请号：US09312713

申请日：1999-05-17

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： A61K3155

CPC分类号： C07D487/04 ,  C07D207/34

摘要： A method for treating a circulatory disease or condition in a mammal, which entails administering to the mammal an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof: wherein the ring P represented by  is a pyrrole ring having the following structure: wherein R1 represents C1-C8 alkyl, C3-C8 cycloalkyl, C4-C8 cycloalkyl-alkyl, C6-C14 aryl or C7-C22 aralkyl, which are optionally substituted; and R2 represents H or C1-C8 alkyl, which is optionally substituted; 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 and Z2 are both H; Z1 represents H and Z2 represents a group OR3, in which R3 represents H, C1-C8 alkyl, or C7-C22 aralkyl, which are optionally substituted; Z1 and Z2 both represent groups SR4, in which R4 represents C1-C8 alkyl or C7-C22 aralkyl, which are optionally substituted; or Z1 and Z2 are combined together to represent O, a group NOR5, in which R5 represents H, or C1-C8 alkyl or C2-C3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C═ or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C═O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E1 and E2 is H or C1-C8 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： 一种用于治疗哺乳动物的循环系统疾病或病症的方法，其需要向哺乳动物施用有效量的式（I）化合物或其药学上可接受的盐：其中由表示的环P是具有以下基团的吡咯环 结构：其中R 1表示任选取代的C 1 -C 8烷基，C 3 -C 8环烷基，C 4 -C 8环烷基 - 烷基，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：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：US06489473B2

公开(公告)日：2002-12-03

申请号：US09801816

申请日：2001-03-09

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： C07D48704

CPC分类号： C07D487/04 ,  C07D207/34

摘要： A method of effecting serotonin-2-receptor antagonism in a mammal in need thereof, which entails administering to the mammal an effective amount of a compound of the formula (I), or a pharmaceutically acceptable salt thereof: wherein ring P, the dashed line, Z1, Z2, A and Y are as defined herein.

摘要翻译： 在有需要的哺乳动物中实现5-羟色胺-2-受体拮抗作用的方法，其需要向哺乳动物施用有效量的式（I）化合物或其药学上可接受的盐：其中环P，虚线 ，Z1，Z2，A和Y如本文所定义。

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：US06294677B1

公开(公告)日：2001-09-25

申请号：US09531141

申请日：2000-03-17

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： C07D33506

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

摘要： An intermediate represented by the following formula (XVIII), wherein A is a sulfur atom or the group —CH═CH—; L is an alkylene group which may be substituted, an alkenylene group which may be substituted, or an alkynylene group which may be substituted; W represents a leaving group selected from the group consisting of a halogen atom, an alkyl sulfonyloxy group, and an aryl sulfonyloxy group, and Z represents the group; (wherein R1 is an alkyl group which may be substituted, an aromatic carbocyclic group which may be substituted, or an aralkyl group which may be substituted, X1, X2, and X3 individually represent an oxygen atom or a sulfur atom, and G represents an ethylene group or a trimethylene group, of which one or more hydrogen atoms of the ethylene group or trimethylene group may be replaced by a halogen atom, alkyl group, aromatic carbocyclic group, aralkyl group, or alkylidene group).

摘要翻译： 由下式（XVIII）表示的中间体，其中A为硫原子或基团-CH = CH-; L可以被取代的亚烷基，可被取代的亚烯基或可被取代的亚炔基; W表示选自卤原子，烷基磺酰氧基和芳基磺酰氧基的离去基团，Z表示基团;（其中，R 1为可被取代的烷基，可以具有芳香族碳环基 或可被取代的芳烷基，X 1，X 2和X 3分别表示氧原子或硫原子，G表示亚乙基的一个或多个氢原子的亚乙基或三亚甲基 或三亚甲基可以被卤素原子，烷基，芳族碳环基，芳烷基或亚烷基取代）。

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。