公开(公告)号：US07208524B2

公开(公告)日：2007-04-24

申请号：US10398383

申请日：2001-10-02

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： A61K31/195 ,  A61K31/18 ,  C07C59/52 ,  C07C307/06

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或任选取代的低级烷基; R 2是二（低级烷基）氨基，低级烷基，环烷基，任选取代的芳基，任选取代的杂环烷基或任选取代的芳族杂环基; T是氧原子，硫原子，磺酰基等; Q是氢原子或任意取代的低级烷基; Z是氢原子，羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗疾病的药剂， 活化凝血因子X，包含其的药物组合物，其药物用途及其中间体。

公开(公告)号：US20060116361A1

公开(公告)日：2006-06-01

申请号：US10398383

申请日：2001-10-02

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： A61K31/44 ,  A61K31/40 ,  A61K31/195

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

公开(公告)号：US07589126B2

公开(公告)日：2009-09-15

申请号：US11553573

申请日：2006-10-27

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： A61K31/195 ,  A61K31/18

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由下列通式表示的5-脒基-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或任意取代的低级烷基; R2是二（低级烷基）氨基，低级烷基，环烷基，任选取代的芳基，任选取代的杂环烷基或任选取代的芳族杂环基; T是氧原子，硫原子，磺酰基等; Q是氢原子或任意取代的低级烷基; Z是氢原子，羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗疾病， 活化凝血因子X，包含其的药物组合物，其药物用途及其中间体。

公开(公告)号：US07217832B2

公开(公告)日：2007-05-15

申请号：US11359430

申请日：2006-02-23

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： C07D265/30 ,  C07D271/113 ,  C07D277/30 ,  C07C255/53 ,  C07C255/63

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

公开(公告)号：US20070105829A1

公开(公告)日：2007-05-10

申请号：US11553573

申请日：2006-10-27

申请人： Kosuke OKAZAKI ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke OKAZAKI ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： A61K31/553 ,  A61K31/55 ,  A61K31/5377 ,  A61K31/445 ,  A61K31/421 ,  A61K31/40 ,  A61K31/18

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或任选取代的低级烷基; R 2是二（低级烷基）氨基，低级烷基，环烷基，任选取代的芳基，任选取代的杂环烷基或任选取代的芳族杂环基; T是氧原子，硫原子，磺酰基等; Q是氢原子或任意取代的低级烷基; Z是氢原子，羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗疾病的药剂， 活化凝血因子X，包含其的药物组合物，其药物用途及其中间体。

公开(公告)号：US20060205812A1

公开(公告)日：2006-09-14

申请号：US11359430

申请日：2006-02-23

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Harunobu Mukaiyama ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Yuji Hoyano ,  Hiroaki Shiohara ,  Norihiko Kikuchi

IPC分类号： A61K31/24 ,  A61K31/195 ,  C07C311/47

CPC分类号： A61K31/18 ,  A61K31/40 ,  A61K31/421 ,  A61K31/445 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/553 ,  C07C311/29 ,  C07C311/37 ,  C07C317/32 ,  C07C2601/14

摘要： The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or an optionally substituted lower alkyl group; R2 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, an optionally substituted heterocycloalkyl group, or an optionally substituted aromatic heterocyclic group; T is an oxygen atom, a sulfur atom, a sulfonyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom, a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或任选取代的低级烷基; R 2是二（低级烷基）氨基，低级烷基，环烷基，任选取代的芳基，任选取代的杂环烷基或任选取代的芳族杂环基; T是氧原子，硫原子，磺酰基等; Q是氢原子或任意取代的低级烷基; Z是氢原子，羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗疾病， 活化凝血因子X，包含其的药物组合物，其药物用途及其中间体。

公开(公告)号：US20060111446A1

公开(公告)日：2006-05-25

申请号：US11246641

申请日：2005-10-11

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

IPC分类号： A61K31/18 ,  C07C311/45

CPC分类号： C07C311/29

摘要： The present invention relates to a 5-amidino-N-(2-aminophenethyl)-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or a lower alkyl group; R2 represents a hydrogen atom, an optionally substituted lower alkyl group, etc.; R3 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group, etc., or a pharmaceutically acceptable salt thereof, which exerts a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-N-（2-氨基苯乙基）-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或低级烷基; R 2表示氢原子，任选取代的低级烷基等; R 3是二（低级烷基）氨基，低级烷基，环烷基等; Q是氢原子或任意取代的低级烷基; Z是氢原子或羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗发生相关疾病的药剂 活化凝血因子X，包含其的药物组合物，其药物用途及其中间体。

公开(公告)号：US07022689B2

公开(公告)日：2006-04-04

申请号：US10486137

申请日：2002-08-08

申请人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

发明人： Kosuke Okazaki ,  Masahiko Uchida ,  Hiroaki Kobayashi ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Ritsu Suzuki

IPC分类号： A01N43/00 ,  A61K31/33

CPC分类号： C07C311/29

摘要： The present invention relates to a 5-amidino-N-(2-aminophenethyl)-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is a hydrogen atom or a lower alkyl group; R2 represents a hydrogen atom, an optionally substituted lower alkyl group, etc.; R3 is a di(lower alkyl)amino group, a lower alkyl group, a cycloalkyl group, etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group, etc., or a pharmaceutically acceptable salt thereof, which exerts a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same, a pharmaceutical use thereof and an intermediate thereof.

摘要翻译： 本发明涉及由以下通式表示的5-脒基-N-（2-氨基苯乙基）-2-羟基苯磺酰胺衍生物：其中R 1是氢原子或低级烷基; R 2表示氢原子，任选取代的低级烷基等; R 3是二（低级烷基）氨基，低级烷基，环烷基等; Q是氢原子或任意取代的低级烷基; Z是氢原子或羟基等，或其药学上可接受的盐，其具有有效和选择性的活化凝血因子X抑制活性，并且可用作预防或治疗发生相关疾病的药剂 活化凝血因子X，包含其的药物组合物，其药物用途和其中间体。

公开(公告)号：US20050143457A1

公开(公告)日：2005-06-30

申请号：US10507616

申请日：2003-03-04

申请人： Harunobu Mukaiyama ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Satoshi Akahane

发明人： Harunobu Mukaiyama ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Satoshi Akahane

IPC分类号： A61P7/02 ,  C07C317/32 ,  A61K31/235 ,  C07C311/35

CPC分类号： C07C317/32

摘要： The present invention provides a novel crystalline form of n-butyl[4-[2-[2-hydroxy-5-(N-hydroxycarbamimidoyl) benzenesulfonylamino]ethyl]-2′-methanesulfonyl-3-yloxy] acetate hydrochloride, pharmaceutical compositions containing the same and their uses, which exhibits excellent inhibitory activities against activated blood coagulation factor X, and is useful for the treatment or prevention of a tromboembolic disease.

摘要翻译： 本发明提供了一种新型的[4- [2- [2-羟基-5-（N-羟基甲脒基）苯磺酰基氨基]乙基] -2'-甲磺酰基-3-基氧基]乙酸盐酸盐的结晶形式，其含有 对活化凝血因子X表现出优异的抑制活性，并且可用于治疗或预防血栓栓塞性疾病。

公开(公告)号：US07256215B2

公开(公告)日：2007-08-14

申请号：US10507616

申请日：2003-03-04

申请人： Harunobu Mukaiyama ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Satoshi Akahane

发明人： Harunobu Mukaiyama ,  Yuichiro Kai ,  Hideki Takeuchi ,  Kenji Yokoyama ,  Yoshihiro Terao ,  Satoshi Akahane

IPC分类号： C07C307/00 ,  A61K31/235

CPC分类号： C07C317/32

摘要： The present invention provides a novel crystalline form of n-butyl[4-[2-[2-hydroxy-5-(N-hydroxycarbamimidoyl) benzenesulfonylamino]ethyl]-2′-methanesulfonyl-3-yloxy] acetate hydrochloride, pharmaceutical compositions containing the same and their uses, which exhibits excellent inhibitory activities against activated blood coagulation factor X, and is useful for the treatment or prevention of a tromboembolic disease.

摘要翻译： 本发明提供了一种新型的[4- [2- [2-羟基-5-（N-羟基甲脒基）苯磺酰基氨基]乙基] -2'-甲磺酰基-3-基氧基]乙酸盐酸盐的结晶形式，其含有 对活化凝血因子X表现出优异的抑制活性，并且可用于治疗或预防血栓栓塞性疾病。