公开(公告)号：US07541341B2

公开(公告)日：2009-06-02

申请号：US10467823

申请日：2002-02-13

申请人： Nobuhiko Fushimi ,  Kazuya Tatani ,  Hideki Fujikura ,  Toshihiro Nishimura ,  Minoru Fujioka ,  Takeshi Nakabayashi ,  Masayuki Isaji

发明人： Nobuhiko Fushimi ,  Kazuya Tatani ,  Hideki Fujikura ,  Toshihiro Nishimura ,  Minoru Fujioka ,  Takeshi Nakabayashi ,  Masayuki Isaji

IPC分类号： A61K31/70 ,  C07H15/00 ,  C07H17/00

CPC分类号： C07H15/203

摘要： The present invention provides glucopyranosyloxybenzylbenzene derivatives represented by the general formula: wherein P represents a hydrogen atom or a group forming a prodrug; R1 represents a hydrogen atom, an optionally substituted amino group, a carbamoyl group, an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, etc.; R2 represents a hydrogen atom or a lower alkyl group; and R3 represents an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, an optionally substituted lower alkylthio group, etc., which have an improved oral absorption, and exert an inhibitory activity in human SGLT2, and therefore are useful as drugs for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, or pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

摘要翻译： 本发明提供由以下通式表示的吡喃葡萄糖氧基苄基苯衍生物：其中P表示氢原子或形成前药的基团; R1表示氢原子，任选取代的氨基，氨基甲酰基，任选取代的低级烷基，任选取代的低级烷氧基等; R2表示氢原子或低级烷基; R3代表任意取代的低级烷基，任意取代的低级烷氧基，任意取代的低级烷硫基等，它们具有改善的口服吸收，并且在人SGLT2中具有抑制活性，因此可用作 预防或治疗与糖尿病，糖尿病并发症或肥胖症等高血糖相关的疾病或其药学上可接受的盐及其药学用途。

公开(公告)号：US07429568B2

公开(公告)日：2008-09-30

申请号：US11247332

申请日：2005-10-12

申请人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

IPC分类号： A01N43/04 ,  A61K31/70 ,  C07H17/00

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02 ,  A61K2300/00

摘要： The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug; one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; R2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

摘要翻译： 本发明提供由以下通式表示的吡喃葡萄糖氧吡唑衍生物：其中R表示氢原子，低级烷基或形成前药的基团; Q和T之一表示由通式表示的基团：（其中P表示氢原子或形成前药的基团），而另一个表示低级烷基或卤代（低级烷基）基团; R 2表示氢原子，低级烷基，低级烷氧基，低级烷硫基，卤代（低级烷基）或卤素原子; 并且条件是当R表示氢原子或低级烷基时，P不表示氢原子，或其药学上可接受的盐，其在人SGLT2中具有抑制活性并具有改善的口服吸收，因此可用作 用于预防或治疗与高血糖相关的疾病如糖尿病，糖尿病并发症或肥胖症的药剂及其药学上可接受的盐及其药学用途。

公开(公告)号：US07271153B2

公开(公告)日：2007-09-18

申请号：US10481013

申请日：2002-06-17

申请人： Toshihiro Nishimura ,  Hideki Fujikura ,  Nobuhiko Fushimi ,  Kazuya Tatani ,  Kenji Katsuno ,  Masayuki Isaji

发明人： Toshihiro Nishimura ,  Hideki Fujikura ,  Nobuhiko Fushimi ,  Kazuya Tatani ,  Kenji Katsuno ,  Masayuki Isaji

IPC分类号： A01N43/04 ,  A61K31/70 ,  C07H15/24

CPC分类号： C07H17/02 ,  Y02P20/55 ,  Y10S514/866 ,  Y10S514/909

摘要： The present invention provides nitrogen-containing heterocyclic derivatives represented by the general formula: wherein X1 and X3 independently represent N or CH; X2 represents N or CR2; X4 represents N or CR3; and with the proviso that one or two of X1, X2, X3 and X4 represent N; R1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group, a lower alkoxy(lower alkoxy)-substituted (lower alkyl) group, a cyclic lower alkyl group, a halo(lower alkyl) group or a group represented by the general formula: HO-A- wherein A represents a lower alkylene group, a lower alkyleneoxy group or a lower alkylenethio group; R2 represents a hydrogen atom, a halogen atom, a lower alkyl group, a cyclic lower alkyl group, a lower alkoxy group, an amino group, a (lower acyl)amino group, a mono(lower alkyl)amino group or a di(lower alkyl)amino group; and R3 represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, or prodrugs thereof which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses and production intermediates thereof.

摘要翻译： 本发明提供由以下通式表示的含氮杂环衍生物：其中X 1和X 3独立地表示N或CH; X 2表示N或CR 2; X 4表示N或CR 3; 并且条件是X 1，X 2，X 3和X 4中的一个或者两个表示N ; R 1表示氢原子，卤素原子，低级烷基，低级烷氧基，低级烷硫基，低级烷氧基取代的（低级烷基），低级烷氧基取代的（低级烷基） 低级烷氧基）基团，低级烷氧基（低级烷氧基） - 取代（低级烷基）基团，环状低级烷基基团，卤代（低级烷基）基团或由通式HO-A-表示的基团，其中A表示 低级亚烷基，低级亚烷基氧基或低级亚烷基硫基; R 2表示氢原子，卤素原子，低级烷基，环状低级烷基，低级烷氧基，氨基，（低级酰基）氨基，单（低级） 烷基）氨基或二（低级烷基）氨基; R 3表示氢原子或低级烷基，或其药学上可接受的盐或其前药，其可用作预防或治疗与高血糖相关的疾病如糖尿病，糖尿病 并发症或肥胖症，包含其的药物组合物及其药物用途和生产中间体。

公开(公告)号：US07189702B2

公开(公告)日：2007-03-13

申请号：US11358400

申请日：2006-02-22

申请人： Toshihiro Nishimura ,  Nobuhiko Fushimi ,  Hideki Fujikura ,  Kenji Katsuno ,  Yoshimitsu Komatsu ,  Masayuki Isaji

发明人： Toshihiro Nishimura ,  Nobuhiko Fushimi ,  Hideki Fujikura ,  Kenji Katsuno ,  Yoshimitsu Komatsu ,  Masayuki Isaji

IPC分类号： A01N43/04 ,  A61K31/70 ,  C07H17/00

CPC分类号： C07H15/203 ,  C07H17/02

摘要： The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein one of Q and T represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; R1 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkenyl group, a cyclic lower alkyl group, etc.; R2 represents a hydrogen atom, an optionally substituted lower alkyl group, a lower alkoxy group, a lower alkenyl group, a cyclic lower alkyl group, a cyclic lower alkoxy group, etc., which exert an excellent inhibitory activity in human SGLT2, and therefore are useful as drugs for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutically acceptable salts thereof or prodrugs thereof, production intermediates thereof and pharmaceutical uses thereof.

摘要翻译： 本发明提供由以下通式表示的吡喃葡萄糖氧吡唑衍生物：其中Q和T之一表示由通式表示的基团，而另一个代表低级烷基或卤代（低级烷基）基团; R 1表示氢原子，任选取代的低级烷基，低级烯基，环状低级烷基等; R 2表示氢原子，任选取代的低级烷基，低级烷氧基，低级烯基，环状低级烷基，环状低级烷氧基等，其具有优异的 因此可用作预防或治疗与糖尿病，糖尿病并发症或肥胖症，糖尿病并发症或肥胖症，糖尿病并发症或肥胖症，其药学上可接受的盐或其前药，与其生产中间体及其药物用途有关的疾病的药物。

公开(公告)号：US07129381B2

公开(公告)日：2006-10-31

申请号：US10978413

申请日：2004-11-02

申请人： Hideki Fujikura ,  Toshihiro Nishimura ,  Nobuhiko Fushimi ,  Kazuya Tatani ,  Norihiko Kikuchi ,  Kenji Katsuno ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Toshihiro Nishimura ,  Nobuhiko Fushimi ,  Kazuya Tatani ,  Norihiko Kikuchi ,  Kenji Katsuno ,  Masayuki Isaji

IPC分类号： C07C15/00 ,  C07C27/10 ,  C07C33/18 ,  C07C39/00

CPC分类号： C07H15/203

摘要： The present invention relates to glucopyranosyl-oxybenzylbenzene derivatives represented by the general formula: wherein R1 represents a hydrogen atom, a hydroxy group, a substituted or unsubstituted amino group, a carbamoyl group, a substituted or unsubstituted(lower alkyl) group, a substituted or unsubstituted(lower alkoxy) group etc.; R2 represents a hydrogen atom or a lower alkyl group; and R3 represents a substituted or unsubstituted(lower alkyl) group, a substituted or unsubstituted(lower alkoxy) group, a substituted or unsubstituted(lower alkylthio) group etc., or pharmaceutically acceptable salts thereof, which have an inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complication or obesity, pharmaceutical compositions comprising the same and intermediates thereof.

摘要翻译： 本发明涉及由以下通式表示的吡喃葡萄糖基 - 氧苄基苯衍生物：其中R 1表示氢原子，羟基，取代或未取代的氨基，氨基甲酰基，取代或未取代的（ 低级烷基）基团，取代或未取代的（低级烷氧基）基团等; R 2表示氢原子或低级烷基; 和R 3表示取代或未取代的（低级烷基）基团，取代或未取代的（低级烷氧基）基团，取代或未取代的（低级烷硫基）等，或其药学上可接受的盐，其中 在人SGLT2中具有抑制活性，并且可用作预防或治疗与高血糖相关的疾病如糖尿病，糖尿病并发症或肥胖症的药剂，包含其的药物组合物及其中间体。

公开(公告)号：US07084123B2

公开(公告)日：2006-08-01

申请号：US10451926

申请日：2001-12-25

申请人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

IPC分类号： A01N43/04 ,  A61K31/70 ,  C07H17/00

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02 ,  A61K2300/00

摘要： The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug: one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; R2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

摘要翻译： 本发明提供由以下通式表示的吡喃葡萄糖氧吡唑衍生物：其中R表示氢原子，低级烷基或形成前药的基团：Q和T之一表示由通式表示的基团：（其中P表示氢 原子或形成前药的基团），而另一个表示低级烷基或卤代（低级烷基）基团; R 2表示氢原子，低级烷基，低级烷氧基，低级烷硫基，卤代（低级烷基）或卤素原子; 并且条件是当R表示氢原子或低级烷基时，P不表示氢原子，或其药学上可接受的盐，其在人SGLT2中具有抑制活性并具有改善的口服吸收，因此可用作 用于预防或治疗与高血糖相关的疾病如糖尿病，糖尿病并发症或肥胖症的药剂及其药学上可接受的盐及其药学用途。

公开(公告)号：US20060094667A1

公开(公告)日：2006-05-04

申请号：US11247332

申请日：2005-10-12

申请人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Takeshi Nakabayashi ,  Masayuki Isaji

IPC分类号： A61K31/7052 ,  C07H17/02

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02 ,  A61K2300/00

摘要： The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug;.one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; R2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo (lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

摘要翻译： 本发明提供由以下通式表示的吡喃葡萄糖氧吡唑衍生物：其中R表示氢原子，低级烷基或形成前药的基团; Q和T表示由以下通式表示的基团：（其中P表示 氢原子或形成前药的基团），而另一个表示低级烷基或卤代（低级烷基）基团; R 2表示氢原子，低级烷基，低级烷氧基，低级烷硫基，卤代（低级烷基）或卤素原子; 并且条件是当R表示氢原子或低级烷基时，P不表示氢原子，或其药学上可接受的盐，其在人SGLT2中具有抑制活性并具有改善的口服吸收，因此可用作 用于预防或治疗与高血糖相关的疾病如糖尿病，糖尿病并发症或肥胖症的药剂及其药学上可接受的盐及其药学用途。

公开(公告)号：US06972283B2

公开(公告)日：2005-12-06

申请号：US10759138

申请日：2004-01-20

申请人： Hideki Fujikura ,  Toshihiro Nishimura ,  Kenji Katsuno ,  Masahiro Hiratochi ,  Akira Iyobe ,  Minoru Fujioka ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Toshihiro Nishimura ,  Kenji Katsuno ,  Masahiro Hiratochi ,  Akira Iyobe ,  Minoru Fujioka ,  Masayuki Isaji

IPC分类号： A61K31/7056 ,  A61P3/04 ,  A61P3/10 ,  C07D231/20 ,  C07H17/02 ,  A61K31/70 ,  A61K31/415 ,  A61K31/7042 ,  C07H17/00

CPC分类号： C07D231/20 ,  C07H17/02 ,  Y10S514/866 ,  Y10S514/909

摘要： The present invention relates to glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R1 represents a hydrogen atom or a lower alkyl group; one of Q1 and T1 represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; and R2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or pharmaceutically acceptable salts thereof, which have an inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of diabetes, diabetic complications or obesity, and to pharmaceutical compositions comprising the same and intermediates thereof.

摘要翻译： 本发明涉及由以下通式表示的吡喃葡萄糖氧吡唑衍生物：其中R 1表示氢原子或低级烷基; Q 1和T 1之一表示由通式表示的基团，而另一个表示低级烷基或卤代（低级烷基）基团; 和R 2表示氢原子，低级烷基，低级烷氧基，低级烷硫基，卤代（低级烷基）基或卤素原子或其药学上可接受的盐，它们具有 在人SGLT2中的抑制活性，并且可用作预防或治疗糖尿病，糖尿病并发症或肥胖症的药剂，以及包含其的药物组合物及其中间体。

公开(公告)号：US20050261206A1

公开(公告)日：2005-11-24

申请号：US11191024

申请日：2005-07-28

申请人： Hideki Fujikura ,  Toshihiro Nishimura ,  Kenji Katsuno ,  Masahiro Hiratochi ,  Akira Iyobe ,  Minoru Fujioka ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Toshihiro Nishimura ,  Kenji Katsuno ,  Masahiro Hiratochi ,  Akira Iyobe ,  Minoru Fujioka ,  Masayuki Isaji

IPC分类号： A61K31/7056 ,  A61P3/04 ,  A61P3/10 ,  C07D231/20 ,  C07H17/02

CPC分类号： C07D231/20 ,  C07H17/02 ,  Y10S514/866 ,  Y10S514/909

摘要： The present invention relates to glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R1 represents a hydrogen atom or a lower alkyl group; one of Q1 and T1 represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; and R2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or pharmaceutically acceptable salts thereof, which have an inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of diabetes, diabetic complications or obesity, and to pharmaceutical compositions comprising the same and intermediates thereof.

公开(公告)号：US20050065098A1

公开(公告)日：2005-03-24

申请号：US10916548

申请日：2004-08-12

申请人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Kazuya Tatani ,  Masayuki Isaji

发明人： Hideki Fujikura ,  Nobuhiko Fushimi ,  Toshihiro Nishimura ,  Kazuya Tatani ,  Masayuki Isaji

IPC分类号： A61K31/7034 ,  A61P3/04 ,  A61P3/10 ,  A61P43/00 ,  C07H15/203 ,  A61K31/70 ,  C07H13/02

CPC分类号： C07H15/203 ,  A61K31/7034

摘要： The present invention relates to glucopyranosyloxy-benzylbenzene derivatives represented by the general formula: wherein P represents a group forming a prodrug; and R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group, which have an improved oral absorption and can exert an excellent inhibitory activity in human SGLT2 in vivo and which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same.

摘要翻译： 本发明涉及由以下通式表示的吡喃葡萄糖氧基 - 苄基苯衍生物：其中P表示形成前药的基团; R代表低级烷基，低级烷氧基，低级烷硫基，低级烷氧基取代的（低级烷基），低级烷氧基取代的（低级烷氧基）或低级烷氧基取代的（低级烷硫基） 其具有改善的口服吸收并且可以在体内在人SGLT2中发挥优异的抑制活性，并且其可用作预防或治疗与高血糖相关的疾病如糖尿病，糖尿病并发症或肥胖症的药剂，以及包含 相同。