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公开(公告)号:US08470829B2
公开(公告)日:2013-06-25
申请号:US11662289
申请日:2005-09-09
申请人: Kazutaka Tachibana , Haruhiko Sato , Masateru Ohta , Mitsuaki Nakamura , Takuya Shiraishi , Hitoshi Yoshino , Takashi Emura , Akie Honma , Etsuro Onuma , Hiromitsu Kawata , Kenji Taniguchi
发明人: Kazutaka Tachibana , Haruhiko Sato , Masateru Ohta , Mitsuaki Nakamura , Takuya Shiraishi , Hitoshi Yoshino , Takashi Emura , Akie Honma , Etsuro Onuma , Hiromitsu Kawata , Kenji Taniguchi
IPC分类号: A61K31/426 , A61K31/454 , A61K31/428 , A61K31/4166 , C07D401/12 , C07D403/12 , C07D277/82 , C07D233/72 , C07D233/70
CPC分类号: C07D417/04 , C07D211/58 , C07D233/74 , C07D233/86 , C07D277/82 , C07D401/04
摘要: An imidazole derivative represented by formula (I): wherein Q is: A is hydrogen, halogen, or a substituted or unsubstituted C1-4 alkyl group; E is independently selected from a C1-6 alkyl group; R2 and R3 are independently selected from C1-6 alkyls; X1 and X2 are independently selected from O and S; Y is selected from a substituted or unsubstituted arylene group and a substituted or unsubstituted divalent 5- or 6-membered monocyclic or 8- to 10-membered condensed heterocyclic group; Z is —CON(—Ra)—, —CO—, —OOO—, —NRa—C(═NH)NRb—, —NRa—C(═N—CN)NRb—, —N(—Ra)COO—, —C(═NH)—, —SO2—, —SO2N(—Ra)—, —SO2NR1—, —N(—Ra)CO—, —N(—Ra)CON(—Rb)—, —N(COR1)CO—, —N(—Ra)SO2—, —N(SO2R1)SO2—, —N(—Ra)— or —N(—Ra)SO2N(—Rb)—; R1 is independently a hydrogen atom, a hydroxyl group, or substituted or unsubstituted group selected from C1-6 alkyl group, heterocyclic group, aryl group, C3-8 cycloalkyl group and C3-8 cycloalkenyl group; or salt or prodrug thereof.
摘要翻译: 由式(I)表示的咪唑衍生物:其中Q是:A是氢,卤素或取代或未取代的C1-4烷基; E独立地选自C 1-6烷基; R2和R3独立地选自C1-6烷基; X1和X2独立地选自O和S; Y选自取代或未取代的亚芳基和取代或未取代的二价5元或6元单环或8至10元稠合杂环基; Z是-CON(-R a) - , - CO - , - OO-,-NR a -C(= NH)NR b - , - NR a -C(= N-CN)NR b - , - N(-R a) ,-C(= NH) - , - SO 2 - , - SO 2 N(-R a) - , - SO 2 NR 1 - , - N(-R a)CO - , - N(-R a)CON(-R b) COR 1)CO - , - N(-R a)SO 2 - , - N(SO 2 R 1)SO 2 - , - N(-R a) - 或-N(-R a)SO 2 N(-R b) R 1独立地为氢原子,羟基或取代或未取代的选自C 1-6烷基,杂环基,芳基,C 3-8环烷基和C 3-8环烯基的基团; 或其盐或前药。
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公开(公告)号:US07807675B2
公开(公告)日:2010-10-05
申请号:US11547158
申请日:2005-04-01
申请人: Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
发明人: Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
IPC分类号: C07D475/00 , A61K31/715
CPC分类号: C08L5/08 , A61K31/519 , A61K47/61 , A61K47/65 , C07D475/08 , C08B37/0072
摘要: An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein methotrexate is conjugated with a hydroxy group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids, and the linker is conjugated with the hyaluronic acid through a carbamate group.
摘要翻译: 本发明的目的是提供一种可用作关节病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。 提供了可用于治疗关节疾病的透明质酸 - 甲氨蝶呤缀合物,其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羟基缀合,并且接头与 透明质酸通过氨基甲酸酯基团。
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公开(公告)号:US20090093414A1
公开(公告)日:2009-04-09
申请号:US11547158
申请日:2005-04-01
申请人: Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
发明人: Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
IPC分类号: A61K31/728 , A61K38/03 , C07K2/00 , C07H3/00 , C07D475/00
CPC分类号: C08L5/08 , A61K31/519 , A61K47/61 , A61K47/65 , C07D475/08 , C08B37/0072
摘要: An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein methotrexate is conjugated with a hydroxy group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids, and the linker is conjugated with the hyaluronic acid through a carbamate group.
摘要翻译: 本发明的目的是提供可用作关节病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。 提供了可用于治疗关节疾病的透明质酸 - 甲氨蝶呤缀合物,其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羟基缀合,并且接头与 透明质酸通过氨基甲酸酯基团。
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公开(公告)号:US20110306615A1
公开(公告)日:2011-12-15
申请号:US11662289
申请日:2005-09-09
申请人: Kazutaka Tachibana , Haruhiko Sato , Masateru Ohta , Mitsuaki Nakamura , Takuya Shiraishi , Hitoshi Yoshino , Takashi Emura , Akie Honma , Etsuro Onuma , Hiromitsu Kawata , Kenji Taniguchi
发明人: Kazutaka Tachibana , Haruhiko Sato , Masateru Ohta , Mitsuaki Nakamura , Takuya Shiraishi , Hitoshi Yoshino , Takashi Emura , Akie Honma , Etsuro Onuma , Hiromitsu Kawata , Kenji Taniguchi
IPC分类号: A61K31/454 , C07D233/74 , C07D417/10 , C07D403/12 , C07D233/86 , C07D413/12 , A61K31/4166 , A61K31/428 , A61K31/496 , A61K31/4439 , A61K31/5377 , A61P35/00 , A61P13/08 , A61Q7/00 , A61P15/00 , A61P17/10 , C07D401/04
CPC分类号: C07D417/04 , C07D211/58 , C07D233/74 , C07D233/86 , C07D277/82 , C07D401/04
摘要: According to the present invention, a compound represented by formula (I): wherein Q is: A is a hydrogen atom, a halogen atom, —ORa or a C1-4 alkyl group which may be substituted by one or more halogen atoms; E is independently selected from a C1-6 alkyl group; m is selected from integers from 0 to 3; R2 and R3 are independently selected from a C1-6 alkyl group; X1 and X2 are independently selected from O and S; Y is selected from an arylene group and a divalent 5- or 6-membered monocyclic or 8- to 10-membered condensed heterocyclic group, wherein the arylene group and the heterocyclic group may be substituted by 1 to 3 substituents independently selected from E1; E1 is independently selected from a hydroxyl group, a halogen atom, a C1-4 alkyl group, a cyano group, a C1-4 alkoky group, a carbamoyl group, a C1-4 alkylcarbamoyl group, a di(C1-4 alkyl)carbamoyl group, an amino group, a C1-4 alkylamino group, a di(C1-4 alkylamino group, a sulfamoyl group, a C1-4 alkylsulfamoyl group and a di(C1-4 alkyl)sulfamoyl group; Z is —CON(—Ra)—, —CO—, —COO—, —NRa—C(═NH)NRb—, —NRa—C(═N—CN)NRb—, —N(—Ra)COO—, —C(═NH)—, —SO2—, —SO2N(—Ra)—, —SO2NR1—, —N(—Ra)CO—, —N(—Ra)CON(—Rb)—, —N(COR1)CO—, —N(—Ra)SO2—, —N(SO2R1)SO2—, —N(—Ra)— or —N(—Ra)SO2N(—Rb)—; R1 is independently a hydrogen atom, a hydroxyl group, a C1-6 alkyl group which may be substituted by one or more substituents, a heterocyclic group which may be substituted by one or more substituents, an aryl group which may be substituted by one or more substituents, a C3-8 cycloalkyl group which may be substituted by one or more substituents or a C3-8 cycloalkenyl group which may be substituted by one or more substituents, or a salt, prodrug or solvate thereof is provided. Furthermore, a pharmaceutical composition containing the compound, and the like are also provided.
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