JP2002500629A - テトラアザ−またはN2S2−錯化剤(complexant)、および放射線診断または放射線治療におけるその使用 - Google Patents
テトラアザ−またはN2S2−錯化剤(complexant)、および放射線診断または放射線治療におけるその使用Info
- Publication number
- JP2002500629A JP2002500629A JP54176898A JP54176898A JP2002500629A JP 2002500629 A JP2002500629 A JP 2002500629A JP 54176898 A JP54176898 A JP 54176898A JP 54176898 A JP54176898 A JP 54176898A JP 2002500629 A JP2002500629 A JP 2002500629A
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- nitrogen
- independently
- compound
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
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Classifications
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- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
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- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
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- A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
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- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.以下の式の化合物であって: ここで: n=1であり; R1およびR2は、独立して、水素、=O(但し、両方ともが=Oではない)、-(CH2)m -Z(ここで、mは0〜10であり、Zは結合基または標的化部分を表す)、および- (CH2)m-W(ここで、mは0〜10であり、Wは加水分解可能な基を表す)から選択さ れるか、またはR1およびR2は一緒になって、環式無水物もしくはベンゼン環を形 成し; R3は、水素、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロ、 -(CH2)m-Zまたは-(CH2)m-Wであり; R4およびR5は、該環の1つ以上の位置で結合し、そして独立して、水素、低級 アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロ、-(CH2)m-Zおよび-(C H2)m-Wから選択され; R6およびR7は、独立して、水素(但し、両方ともが水素ではない)、低級アル キル、アルコキシ、ハロゲン、ヒドロキシル、ニトロ、-(CH2)m-Z、-(CH2)m-Wお よび から選択され、 ここで、Qは、金属イオンと配位し得る多価酸官能基を表し、p=0〜1であり ;R12およびR13は、独立して、水素、ヒドロキシル、カルボキシル、ホスホン酸 、および1〜10個の炭素原子を有する炭化水素基、および該酸基の生理学的に受 容可能な塩から選択され; X、X'、YおよびY'は、独立して、炭素、窒素、酸素およびイオウから選択され て、独立して、5または6員芳香環を形成し、ここで、残りの環原子が炭素であ り; AおよびA'は、独立して、イオウおよび窒素から選択され、ここでイオウは、 水素またはイオウ保護基を有するか、またはここでAおよびA'は両方ともイオウ であり、AおよびA'は結合によって互いに連結され得;ここで、窒素は水素を有 し得るか;またはここで、AまたはA'は窒素であり、AはR8もしくはR10または両 方を有し得、かつA'はR9もしくはR11または両方を有し得、ここでR8、R9、R10お よびR11は、独立して、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、 ニトロ、-(CH2)m-Z、-(CH2)m-Wおよび から選択されるか;またはR8およびR10は連結して環式無水物を形成し得るか、 もしくはR9およびR11は連結して環式無水物を形成し得るか;またはAおよびA'が 両方とも窒素である場合、R10およびR11は連結してTを形成し得、ここでTは、 であり、nは0〜1であり、R1'およびR2'は、独立して、水素、=O(但し、両方 ともが=Oではない)、-(CH2)m-Zから選択されるか、またはR1'およびR2'は、一 緒になって、環式無水物もしくはベンゼン環を形成し;R3'は、水素、低級アル キル、アルコキシ、ハロゲン、ヒドロキシル、ニトロ、-(CH2)m-Zもしくは-(CH2 )m-Wであり;そして 少なくとも1つのZ、WまたはQを有する、化合物。 2.請求項1に記載の化合物であって、ここで: R1およびR2は、独立して、水素、=O(両方ともが=Oではない)、および-(CH2)m -Z(ここでmは0〜10であり、そしてZは結合基または標的化部分を表す)から 選択されるか、またはR1およびR2は、一緒になって、環式無水物もしくはベンゼ ン環を形成し; R3は、水素、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロま たは-(CH2)m-Zであり; R4およびR5は、該環の1つ以上の位置で結合し、そして独立して、水素、低級 アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロおよび-(CH2)m-Zから 選択され; R6およびR7は、独立して、水素(但し、両方ともが水素ではない)、低級アル キル、アルコキシ、ハロゲン、ヒドロキシル、ニトロおよび-(CH2)m-Z、または から選択され; X、X'、YおよびY'は、独立して、炭素、窒素およびイオウから選択されて、5 または6員芳香環を形成し、ここで、残りの環原子が炭素であり; AおよびA'は、独立して、イオウおよび窒素から選択され、ここでイオウは、 水素またはイオウ保護基を有するか、またはここでAおよびA'は両方ともイオウ であり、AおよびA'は結合によって互いに連結され得;ここで、窒素は水素を有 し得るか;またはここで、AまたはA'は窒素であり、AはR8もしくはR10または両 方を有し得、かつA'はR9もしくはR11または両方を有し得、ここでR8、R9、R10お よびR11は、独立して、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、 ニトロ、-(CH2)m-Zおよび から選択されるか;またはR8およびR10は連結して環式無水物を形成し得るか、 もしくはR9およびR11は連結して環式無水物を形成し得るか;またはAおよびA'が 両方とも窒素である場合、R10およびR11は連結してTを形成し得、ここでTは、 であり、nは0〜1であり、R1'およびR2'は、独立して、水素、=O(但し、両方 ともが=Oではない)、および-(CH2)m-Zから選択されるか;またはR1'およびR2' は、一緒になって、環式無水物もしくはベンゼン環を形成し;そしてR3'は、水 素、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロもしくは-(CH2 )m-Zであり;そして 少なくとも1つのZまたはQを有する、化合物。 3.請求項2に記載の化合物であって、ここでn=1であり;R1、R2、R3は水素 であり;R4およびR5は、独立して、水素および-(CH2)m-Zから選択され;R6およ びR7は、 であり、ここでp=0であり、R12およびR13は水素であり、Qは金属イオンと配位 し得る多価酸官能基であり;AおよびA'は両方とも窒素であり、ここでAはR8もし くはR10または両方を有し、A'はR9もしくはR11または両方を有し、ここでR8、R9 、R10、R11は であり、ここでQは、独立して、ホスホン酸およびカルボン酸から選択され、p= 0であり、そしてR12およびR13は水素であり;またはR8およびR10は連結して環 式無水物を形成し得るか、もしくはR9およびR11は連結して環式無水物を形成し 得;もしくはR10およびR11は連結してTを形成し得、ここでnは1であり、そして R1'、R2'およびR3'は水素である、化合物。 4.請求項2に記載の化合物であって、ここで、n=0であり;R1およびR2は、 一緒になって、ベンゼン環を形成し;R4およびR5は、独立して、水素および-(CH2 )m-Zから選択され;R6およびR7は、 であり、ここでQは、独立して、ホスホン酸およびカルボン酸から選択され、p= 0であり、そしてR12およびR13は水素であり;AおよびA'は両方とも窒素であり 、そしてR10およびR11は連結してTを形成し、ここでnは0であり、R1'およびR2' は、一緒になって、ベンゼン環を形成し、そしてR8およびR9は、 であり、ここでQは、独立して、ホスホン酸およびカルボン酸から選択され得、p =0であり、そしてR12およびR13は水素である、化合物。 5.請求項2に記載の化合物であって、ここでn=1であり;R1、R2およびR3は 水素であり;R4およびR5は、独立して、水素および-(CH2)m-Zから選択され;R6 およびR7は、 であり、ここで、Qは、独立して、ホスホン酸およびカルボン酸から選択され、p =0であり、そしてR12およびR13は水素であり;AおよびA'は両方とも窒素であ り、R8、R9、R10およびR11は、独立して、-(CH2)m-Z(ここで、mは0〜10であり 、Zは標的化部分である)、ならびにから選択され、ここでQは、独立して、ホスホン酸およびカルボン酸から選択さ れ、p=0であり、そしてR12およびR13は水素であるが、但し、該化合物は、少 なくとも1つのZを有する、化合物。 6.Zが、抗体フラグメント、ビオチンまたはアネキシンから選択される標的化 部分である、請求項5に記載の化合物。 7.請求項1に記載の化合物であって、ここで: R1およびR2は、独立して、水素、=O(但し、両方ともが=Oではない)、および -(CH2)m-W(ここで、mは0〜10であり、Wは加水分解可能な基を表す)から選択 されるか、またはR1およびR2は一緒になって、環式無水物もしくはベンゼン環を 形成し; R3は、水素、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロま たは-(CH2)m-Wであり; R4およびR5は、該環の1つ以上の位置で結合し、そして独立して、水素、低級 アルキル、アルコキシ、ハロゲン、ヒドロキシル、ニトロおよび-(CH2)m-Wから 選択され; R6およびR7は、独立して、水素、低級アルキル、アルコキシ、ハロゲン、ヒド ロキシル、ニトロ、-(CH2)m-Wおよび から選択され; AおよびA'は、独立して、イオウおよび窒素から選択され、ここでイオウは、 水素またはイオウ保護基を有し得るか、またはここでAおよびA'は両方ともイオ ウであり、AおよびA'は結合によって互いに連結され得;ここで、窒素は水素を 有し得るか;またはここで、AまたはA'は窒素であり、AはR8もしくはR10または 両方を有し得、かつA'はR9もしくはR11または両方を有し得、ここでR8、R9、R10 およびR11は、独立して、低級アルキル、アルコキシ、ハロゲン、ヒドロキシル 、ニトロ、-(CH2)m-Wおよび から選択されるか;またはR8およびR10は連結して環式無水物を形成し得るか、 もしくはR9およびR11は連結して環式無水物を形成し得るか;またはAおよびA'が 両方とも窒素である場合、R10およびR11は連結してTを形成し得、ここでTは、 であり、nは0〜1であり、R1'およびR2'は、独立して、水素、=O(但し、両方 ともが=Oではない)、-(CH2)m-W(ここで、mは0〜10であり、Wは加水分解可能 な基を表す)から選択されるか、またはR1'およびR2'は、一緒になって、環式無 水物もしくはベンゼン環を形成し;そしてR3'は、水素、低級アルキル、アルコ キシ、ハロゲン、ヒドロキシル、ニトロおよび-(CH2)m-Wであり;そして 少なくとも1つのWを有する、化合物。 8.請求項7に記載の化合物であって、ここでn=1であり;R1、R2およびR3は 水 素であり;R4およびR5は、独立して、水素および-(CH2)m-Wから選択され;R6お よびR7は、 であり、ここで、Qは、独立して、ホスホン酸およびカルボン酸から選択され、p =0であり、そしてR12およびR13は水素であり;AまたはA'は、独立して、保護 基を含むイオウ、および窒素(但し、AおよびA'の両方がイオウではない)から 選択され得、そして、AまたはA'が窒素である場合、R8およびR10は、独立して、 水素および-(CH2)m-W(ここで、mは1〜10であり、Wは加水分解可能な基を表す )から選択され、但し、両方ともが水素ではない、化合物。 9.Wが、エステル、カルバメートおよびニトリルからなる群から選択される、 請求項8に記載の化合物。 10.X、X'、YおよびY'がすべて炭素である、請求項2から9のいずれか1項に 記載の化合物。 11.実施例IからXIのいずれか1つの表題化合物。 12.放射性核種金属またはその酸化物もしくは窒化物を有する、請求項1から 11のいずれか1項に記載の化合物を含む、錯体。 13.請求項12に記載の錯体であって、前記放射性核種が、テクネチウム、銅 、レニウム、鉛、ビスマス、ルテニウム、ロジウム、イットリウム、サマリウム 、インジウム、金、ガドリニウム、ホルミウム、ルテチウム、イッテルビウムま たはパラジウムの放射性核種である、錯体。 14.前記放射性核種が、テクネチウム、ルテニウム、インジウム、ホルミウム またはイットリウムの放射性核種である、請求項13に記載の錯体。 15.請求項13に記載の錯体であって、前記放射性核種が、64Cu、67Cu、90Y 、97Ru、99mTc、105Rh、109Pd、111In、153Sm、159Gd、166Ho、175Yb、177Lu、1 86 Re、188Re、198Au、199Au、203Pb、212Pbまたは212Biである、錯体。 16.前記放射性核種が、99mTc、186Re、188Re、111In、166Hoまたは90Yである 、請求項14に記載の錯体。 17.診断法または治療法において使用するための、請求項12、13、14、 15または16のいずれか1項に記載の錯体。 18.医薬の製造において使用するための、請求項12、13、14、15また は16のいずれか1項に記載の錯体。
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1997
- 1997-03-28 US US08/829,533 patent/US6005083A/en not_active Expired - Lifetime
-
1998
- 1998-03-26 WO PCT/US1998/005858 patent/WO1998043678A2/en active IP Right Grant
- 1998-03-26 EP EP07001523A patent/EP1813607A3/en not_active Withdrawn
- 1998-03-26 CA CA002284653A patent/CA2284653C/en not_active Expired - Fee Related
- 1998-03-26 EP EP98912032A patent/EP0971748B1/en not_active Expired - Lifetime
- 1998-03-26 JP JP54176898A patent/JP2002500629A/ja not_active Ceased
- 1998-03-26 ES ES98912032T patent/ES2281927T3/es not_active Expired - Lifetime
- 1998-03-26 DE DE69837038T patent/DE69837038T2/de not_active Expired - Lifetime
-
1999
- 1999-05-12 US US09/310,900 patent/US6177551B1/en not_active Expired - Fee Related
- 1999-05-12 US US09/310,455 patent/US6187910B1/en not_active Expired - Fee Related
-
2000
- 2000-11-28 US US09/724,834 patent/US6528627B1/en not_active Expired - Fee Related
-
2003
- 2003-01-17 US US10/346,311 patent/US6936700B2/en not_active Expired - Fee Related
-
2005
- 2005-02-18 US US11/061,110 patent/US7268220B2/en not_active Expired - Fee Related
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US6936700B2 (en) | 2005-08-30 |
CA2284653A1 (en) | 1998-10-08 |
US7674886B2 (en) | 2010-03-09 |
EP1813607A3 (en) | 2007-08-15 |
CA2284653C (en) | 2008-07-29 |
WO1998043678B1 (en) | 1999-04-01 |
US20080227961A1 (en) | 2008-09-18 |
US20050276754A1 (en) | 2005-12-15 |
WO1998043678A3 (en) | 1999-03-04 |
US6528627B1 (en) | 2003-03-04 |
US6177551B1 (en) | 2001-01-23 |
EP0971748B1 (en) | 2007-02-07 |
US6187910B1 (en) | 2001-02-13 |
DE69837038D1 (de) | 2007-03-22 |
EP0971748A2 (en) | 2000-01-19 |
DE69837038T2 (de) | 2007-07-12 |
WO1998043678A2 (en) | 1998-10-08 |
US6005083A (en) | 1999-12-21 |
EP1813607A2 (en) | 2007-08-01 |
US20030158393A1 (en) | 2003-08-21 |
ES2281927T3 (es) | 2007-10-01 |
US7268220B2 (en) | 2007-09-11 |
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