公开(公告)号：US08022191B2

公开(公告)日：2011-09-20

申请号：US11498053

申请日：2006-08-03

申请人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

发明人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

IPC分类号： A61K38/18

CPC分类号： C07K14/505 ,  A61K38/1816 ,  A61K47/60

摘要： The present invention provides a polyethylene glycol-conjugated erythropoietin (PEG-conjugated EPO) prepared by PEG conjugation on the lysine residue at position 52 of native erythropoietin (native EPO). In order to achieve more sustained efficacy without losing physiological activities of native EPO, a glycoprotein rich in sugar chains, there has been a need to develop a PEG-conjugated EPO with significantly sustained efficacy by introducing a controlled number of PEG molecules at controlled positions. This PEG-conjugated EPO addresses such a need and provides more sustained efficacy.

摘要翻译： 本发明提供通过PEG缀合在天然促红细胞生成素（天然EPO）的52位的赖氨酸残基上制备的聚乙二醇缀合的促红细胞生成素（PEG-缀合的EPO）。 为了获得更持久的功效而不损失富含糖链的糖蛋白的天然EPO的生理活性，需要通过在受控位置引入受控数量的PEG分子来开发具有显着持续功效的PEG-缀合的EPO。 这种PEG结合的EPO解决了这种需要并提供更持久的功效。

公开(公告)号：US20060276634A1

公开(公告)日：2006-12-07

申请号：US11498053

申请日：2006-08-03

申请人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

发明人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

IPC分类号： A61K38/18 ,  C07K14/51

CPC分类号： C07K14/505 ,  A61K38/1816 ,  A61K47/60

摘要： The present invention provides a polyethylene glycol-conjugated erythropoietin (PEG-conjugated EPO) prepared by PEG conjugation on the lysine residue at position 52 of native erythropoietin (native EPO). In order to achieve more sustained efficacy without losing physiological activities of native EPO, a glycoprotein rich in sugar chains, there has been a need to develop a PEG-conjugated EPO with significantly sustained efficacy by introducing a controlled number of PEG molecules at controlled positions. This PEG-conjugated EPO addresses such a need and provides more sustained efficacy.

摘要翻译： 本发明提供通过PEG缀合在天然促红细胞生成素（天然EPO）的52位的赖氨酸残基上制备的聚乙二醇缀合的促红细胞生成素（PEG-缀合的EPO）。 为了获得更持久的功效而不损失富含糖链的糖蛋白的天然EPO的生理活性，需要通过在受控位置引入受控数量的PEG分子来开发具有显着持续功效的PEG-缀合的EPO。 这种PEG结合的EPO解决了这种需要并提供更持久的功效。

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.

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。

公开(公告)号：US07271188B2

公开(公告)日：2007-09-18

申请号：US10560281

申请日：2004-06-11

申请人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

发明人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

IPC分类号： A61K31/4166 ,  C07D233/86 ,  C07C311/03

CPC分类号： C07D233/86

摘要： The present invention provides a compound represented by formula (I):[Formula 1] wherein n is an integer selected from 1 to 20, and R1 and R2, which may be the same or different, each represent a hydrogen atom, or a linear or branched C1-C6 alkyl group, or a salt, a prodrug or a solvate thereof, as well as a drug, a pharmaceutical composition containing the compound, and the like.

摘要翻译： 本发明提供由式（I）表示的化合物：[式1]其中n是选自1至20，R 1和R 2的整数，其中 可以相同或不同，各自表示氢原子或直链或支链C 1 -C 6烷基，或其盐，前药或溶剂合物 ，以及药物，含有该化合物的药物组合物等。

公开(公告)号：US20060135583A1

公开(公告)日：2006-06-22

申请号：US10560281

申请日：2004-06-11

申请人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

发明人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

IPC分类号： A61K31/4166 ,  C07D233/76

CPC分类号： C07D233/86

摘要： The present invention provides a compound represented by formula (I): wherein n is an integer selected from 1 to 20, and R1 and R2, which may be the same or different, each represent a hydrogen atom, or a linear or branched C1-C6 alkyl group, or a salt, a prodrug or a solvate thereof, as well as a drug, a pharmaceutical composition containing the compound, and the like.

摘要翻译： 本发明提供由式（I）表示的化合物：其中n是选自1至20的整数，R 1和R 2可以相同 或不同的，各自表示氢原子或直链或支链C 1 -C 6烷基，或其盐，前药或溶剂合物，以及 药物，含有该化合物的药物组合物等。

公开(公告)号：US07803826B2

公开(公告)日：2010-09-28

申请号：US11659369

申请日：2005-08-03

申请人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

发明人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

IPC分类号： A61K31/4166 ,  C07D233/40

CPC分类号： C07D233/86 ,  C07D233/76

摘要： The present invention provides a compound represented by formula (I): wherein n is an integer selected from 1 to 20, Q is A is cyano or the like; B is hydrogen, halogen, or the like; X1 and X2 are each independently selected from O and S; E is a C1-4 alkyl group; and R1, R2, R3 and R4 are each independently selected from a hydrogen atom and a C1-C6 alkyl group, and a drug, a pharmaceutical composition containing the compound, and the like.

摘要翻译： 本发明提供由式（I）表示的化合物：其中n是选自1至20的整数，Q是A是氰基等; B是氢，卤素等; X1和X2各自独立地选自O和S; E是C 1-4烷基; R 1，R 2，R 3和R 4各自独立地选自氢原子和C 1 -C 6烷基，以及药物，含有该化合物的药物组合物等。

公开(公告)号：US20070249697A1

公开(公告)日：2007-10-25

申请号：US11659369

申请日：2005-08-03

申请人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

发明人： Kazutaka Tachibana ,  Haruhiko Sato ,  Masateru Ohta ,  Mitsuaki Nakamura ,  Takuya Shiraishi ,  Ikuhiro Imaoka ,  Hitoshi Yoshino ,  Masahiro Nagamuta ,  Hiromitsu Kawata

IPC分类号： A61K31/4164 ,  A61P5/26 ,  C07D233/00

CPC分类号： C07D233/86 ,  C07D233/76

摘要： The present invention provides a compound represented by formula (I): wherein n is an integer selected from 1 to 20, Q is A is cyano or the like; B is hydrogen, halogen, or the like; X1 and X2 are each independently selected from O and S; E is a C1-4 alkyl group; and R1, R2, R3 and R4 are each independently selected from a hydrogen atom and a C1-C6 alkyl group, and a drug, a pharmaceutical composition containing the compound, and the like.

摘要翻译： 本发明提供由式（I）表示的化合物：其中n是选自1至20的整数，Q是A是氰基等; B是氢，卤素等; X 1和X 2各自独立地选自O和S; E是C 1-4烷基; 且R 1，R 2，R 3和R 4各自独立地选自氢原子和 C 1 -C 6烷基，以及药物，含有该化合物的药物组合物等。