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1. 发明授权

US08470829B2 Imidazolidine derivative and use thereof 失效
标题翻译：咪唑烷衍生物及其用途
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。

2. 发明申请

US20110306615A1 NOVEL IMIDAZOLIDINE DERIVATIVE AND USE THEREOF 失效
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.

3. 发明授权

US07803826B2 Imidazolidine derivatives 有权
标题翻译：咪唑烷衍生物
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。

4. 发明申请

US20070249697A1 Novel Imidazolidine Derivatives 有权
标题翻译：新型咪唑烷衍生物
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。

5. 发明授权

US07271188B2 Imidazolidine derivatives 失效
标题翻译：咪唑烷衍生物
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。

6. 发明申请

US20060135583A1 Imidazolidine derivatives 失效
标题翻译：咪唑烷衍生物
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。

7. 发明申请

US20090275623A1 ALPHA-AMINO ACID DERIVATIVES AND MEDICAMENTS CONTAINING THE SAME AS AN ACTIVE INGREDIENT 有权
标题翻译： ALPHA-氨基酸衍生物和含有其作为活性成分的药物
公开(公告)号：US20090275623A1
公开(公告)日：2009-11-05
申请号：US12306901
申请日：2007-06-29
申请人： Kazuhiko Ohrai , Michiaki Adachi , Koji Toyama , Takanori Shimizu , Keishi Hayashi , Masataka Minami , Yoshiyuki Suzuki , Masakazu Sugiyama , Masateru Ohta , Shojiro Kadono , Takuya Shiraishi , Haruhiko Sato , Yoshiaki Watanabe , Nobuya Ishii , Masahiro Sakaitani , Masami Hasegawa
发明人： Kazuhiko Ohrai , Michiaki Adachi , Koji Toyama , Takanori Shimizu , Keishi Hayashi , Masataka Minami , Yoshiyuki Suzuki , Masakazu Sugiyama , Masateru Ohta , Shojiro Kadono , Takuya Shiraishi , Haruhiko Sato , Yoshiaki Watanabe , Nobuya Ishii , Masahiro Sakaitani , Masami Hasegawa
IPC分类号： A61K31/429 , C07D513/04 , A61P9/04 , A61P35/00
CPC分类号： C07D513/04
摘要： The present invention provides novel α-amino acid derivatives of formula (1): (wherein, R1, R2, R3, R4, X and Y are as defined in the claims) or pharmaceutically acceptable salts, prodrugs or solvates thereof. The derivatives of formula (1) have βARK1 inhibitory activity and are useful for preventing or treating heart failure. Moreover, the derivatives of formula (1) also have antitumor activity, particularly dual inhibitory activity on Aurora kinase and CDK, and are useful for cell proliferative diseases such as cancer.
摘要翻译：本发明提供新的式（1）的α-氨基酸衍生物：（其中，R 1，R 2，R 3，R 4，X和Y如权利要求中所定义）或其药学上可接受的盐，前药或溶剂合物。式（1）的衍生物具有βARK1抑制活性，可用于预防或治疗心力衰竭。此外，式（1）的衍生物还具有抗肿瘤活性，特别是对Aurora激酶和CDK的双重抑制活性，并且可用于细胞增殖性疾病如癌症。

8. 发明授权

US07879887B2 α-amino acid derivatives and medicaments containing the same as an active ingredient 有权
标题翻译： α-氨基酸衍生物和含有活性成分的药物
公开(公告)号：US07879887B2
公开(公告)日：2011-02-01
申请号：US12306901
申请日：2007-06-29
申请人： Kazuhiko Ohrai , Michiaki Adachi , Koji Toyama , Takanori Shimizu , Keishi Hayashi , Masataka Minami , Yoshiyuki Suzuki , Masakazu Sugiyama , Masateru Ohta , Shojiro Kadono , Takuya Shiraishi , Haruhiko Sato , Yoshiaki Watanabe , Nobuya Ishii , Masahiro Sakaitani , Masami Hasegawa
发明人： Kazuhiko Ohrai , Michiaki Adachi , Koji Toyama , Takanori Shimizu , Keishi Hayashi , Masataka Minami , Yoshiyuki Suzuki , Masakazu Sugiyama , Masateru Ohta , Shojiro Kadono , Takuya Shiraishi , Haruhiko Sato , Yoshiaki Watanabe , Nobuya Ishii , Masahiro Sakaitani , Masami Hasegawa
IPC分类号： C07D513/04 , A61K31/429
CPC分类号： C07D513/04
摘要： The present invention provides novel α-amino acid derivatives of formula (1): (wherein, R1, R2, R3, R4, X and Y are as defined in the claims) or pharmaceutically acceptable salts, prodrugs or solvates thereof. The derivatives of formula (1) have βARK1 inhibitory activity and are useful for preventing or treating heart failure. Moreover, the derivatives of formula (1) also have antitumor activity, particularly dual inhibitory activity on Aurora kinase and CDK, and are useful for cell proliferative diseases such as cancer.
摘要翻译：本发明提供新的式（1）的α-氨基酸衍生物：其中R1，R2，R3，R4，X和Y如权利要求中所定义）或其药学上可接受的盐，前药或溶剂合物。式（1）的衍生物具有ARK1抑制活性，可用于预防或治疗心力衰竭。此外，式（1）的衍生物还具有抗肿瘤活性，特别是对极光激酶和CDK的双重抑制活性，并且可用于细胞增殖性疾病如癌症。

9. 发明申请

US20090093414A1 Hyaluronic Acid-Methotrexate Conjugate 有权
标题翻译：透明质酸 - 甲氨蝶呤结合物
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。

10. 发明授权

US4791209A Furobenzisoxazole derivatives 失效
标题翻译：呋喃苯并恶唑衍生物
公开(公告)号：US4791209A
公开(公告)日：1988-12-13
申请号：US860210
申请日：1986-05-06
申请人： Haruhiko Sato , Hiroshi Koga , Takashi Dan , Etsuro Onuma
发明人： Haruhiko Sato , Hiroshi Koga , Takashi Dan , Etsuro Onuma
IPC分类号： C07D498/04 , A61K31/42
CPC分类号： C07D498/04
摘要： Novel furobenzisoxazole derivatives of the formula (I): ##STR1## (wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 which may be the same or different represent a hydrogen atom, a halogen atom, or a lower alkyl group having 1-4 carbon atoms; R.sub.5 is a hydroxymethyl group, a carboxyl group or a lower alkoxy carbonyl group having 1-3 carbon atoms; and X is a sulfur atom or a --CH.dbd.CH-- group), as well as intoxic salts thereof when R.sub.5 is a carboxyl group, and process for preparing the same are disclosed.The derivatives of formula (I) and nontoxic salts thereof have hypotensive, uricosuric and diuretic activities and hence ae useful as therapeutics for treating hyperuricemia, edema and hypertension.
摘要翻译：式（I）的新型呋喃苯并异恶唑衍生物：其中R 1，R 2，R 3和R 4可以相同或不同，表示氢原子，卤素原子或具有1-4个碳原子的低级烷基碳原子; R5是羟基甲基，羧基或具有1-3个碳原子的低级烷氧基羰基; X是硫原子或-CH = CH-基团），以及当其为R5时的中性盐羧基，及其制备方法。式（I）的衍生物及其无毒盐具有降血压，尿酸和利尿活性，因此可用作治疗高尿酸血症，水肿和高血压的治疗剂。

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