JP2006503096A - I型光線療法用のアゾ化合物 - Google Patents
I型光線療法用のアゾ化合物 Download PDFInfo
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- JP2006503096A JP2006503096A JP2004545327A JP2004545327A JP2006503096A JP 2006503096 A JP2006503096 A JP 2006503096A JP 2004545327 A JP2004545327 A JP 2004545327A JP 2004545327 A JP2004545327 A JP 2004545327A JP 2006503096 A JP2006503096 A JP 2006503096A
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- Prior art keywords
- receptor binding
- group
- binding molecule
- hydrogen
- alkyl
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Abstract
Description
本発明は、一般的に光線療法(phototherapy)で使用するための新規アゾバイオコンジュゲート(bioconjugate)に関する。
臨床実務における可視および近赤外(NIR)光の使用は、急速に成長している。電磁スペクトルの可視、NIRまたは長波長(UV−A、>350nm)領域で吸光または発光する化合物は、光学的断層撮影、内視鏡的可視化および光線療法に潜在的に有用である。しかしながら、生物医学光学の主要な利点は、その治療的潜在能力にある。光線療法は、内外両側の各種表面病変の処置に安全かつ効果的な手法であると立証されてきた。その有効性は、放射線療法のそれに匹敵するが、重要な非標的器官に対する有害な放射性毒性がない。
本発明は、この要望に取り組み、電磁スペクトルの低エネルギー、紫外、可視、近赤外(NIR)領域で吸光し、腫瘍および他の病変の光線療法に使用される新規アゾ誘導体およびそれらのバイオコンジュゲートを開示する。より具体的には、本発明は、式1
を有するアゾ化合物を開示する。
図1は、本発明の化合物の活性化の図解経路である。
図2は、環状アゾキサンテン誘導体合成の図解経路である。
図3は、アゾアクリジン誘導体合成の図解経路である。
図4は、アゾクマリン誘導体合成の図解経路である。
本発明は、腫瘍および他の病変の光線療法のための新規アゾ誘導体およびそのバイオコンジュゲートを開示する。
アゾクマリン−ボンベシン(7−14)コンジュゲートの合成
Applied Biosystems 販売のペプチド合成機(Model 432A SYNERGY Peptide Synthesizer)を用いて、フルオレニルメトキシカルボニル(Fmoc)固相ペプチド合成戦略によりペプチドを製造した。第一のペプチドカートリッジは、25−:モルスケールのアミド樹脂を予め載せた Wang 樹脂を含有した。アミノ酸カートリッジをペプチド合成機に設置し、CからN末端位置へ生成物を合成した。
Claims (8)
- 式
の化合物。 - 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6、およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−C=Oであり;Yが−CR10R11であり;Zが−CR12R13であり;R10ないしR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、熱感受性バクテリオエンドトキシン(ST)受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、コレシストキニン(CCK)受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが−C=Oであり;Zが、−CR12R13、−O−および−NR3からなる群から選択され;R8、R9、R12およびR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが、−CR10R11、−O−および−NR3からなる群から選択され;Zが−C=Oであり;R8ないしR11が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが−CR10R11であり;Zが−CR12R13であり;R8およびR10が、一緒になってベンゼン環を形成し;R9およびR11が、炭素−炭素結合を形成する基であり;R12およびR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが−CR10R11であり;Zが−O−であり;R8およびR10が、一緒になってベンゼン環を形成し;R9およびR11が、炭素−炭素結合を形成する基であり;R12およびR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが−CR10R11であり;Zが−NR3であり;R8およびR10が、一緒になってベンゼン環を形成し;R9およびR11が、炭素−炭素結合を形成する基であり;R12およびR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
- 式中、Qが−CR1R2であり;R1およびR2が、水素およびC1−C10アルキルからなる群から独立して選択され;R5、R6およびR7が、水素、ヒドロキシル、−SO3Hおよび−(CH2)aCO2Hからなる群から独立して選択され;Xが−CR8R9であり;Yが−CR10R11であり;Zが−C=Oであり;R8およびR10が、一緒になってベンゼン環を形成し;R9およびR11が、炭素−炭素結合を形成する基であり;R12およびR13が、水素、C1−C10アルキル、C5−C10アリールおよび−(CH2)aCO2Hからなる群から独立して選択され;Eが、ソマトスタチン受容体結合分子、ST受容体結合分子、ニューロテンシン受容体結合分子、ボンベシン受容体結合分子、CCK受容体結合分子、ステロイド受容体結合分子および炭水化物受容体結合分子からなる群から選択され;aが、独立して0ないし6の範囲で変動する、請求項1に記載の化合物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/272,123 US6747151B2 (en) | 2001-05-04 | 2002-10-15 | Azo compounds for type I phototherapy |
PCT/US2003/032699 WO2004035536A2 (en) | 2002-10-15 | 2003-10-14 | Azo compounds for type i phototherapy |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2006503096A true JP2006503096A (ja) | 2006-01-26 |
Family
ID=32106426
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2004545327A Pending JP2006503096A (ja) | 2002-10-15 | 2003-10-14 | I型光線療法用のアゾ化合物 |
Country Status (6)
Country | Link |
---|---|
US (1) | US6747151B2 (ja) |
EP (1) | EP1551461A4 (ja) |
JP (1) | JP2006503096A (ja) |
AU (1) | AU2003279973B2 (ja) |
CA (1) | CA2502211A1 (ja) |
WO (1) | WO2004035536A2 (ja) |
Families Citing this family (10)
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US7226577B2 (en) | 2003-01-13 | 2007-06-05 | Bracco Imaging, S. P. A. | Gastrin releasing peptide compounds |
US20050095283A1 (en) * | 2003-09-16 | 2005-05-05 | Aphios Corporation | Compositions and methods for topically treating diseases |
EP1926497A2 (en) * | 2005-07-05 | 2008-06-04 | Université de Lausanne | Use of a photosensitizing agent in the treatment or prevention of an inflammation-associated disorder in the gastrointestinal tract of a mammal |
EP2134367A2 (en) * | 2007-03-01 | 2009-12-23 | Mallinckrodt Inc. | Integrated photoactive peptides and uses thereof |
WO2009012109A2 (en) * | 2007-07-13 | 2009-01-22 | Emory University | Cyanine-containing compounds for cancer imaging and treatment |
CN102099059B (zh) * | 2008-06-13 | 2015-09-23 | 西塞医疗中心 | 用于癌症靶向治疗的小分子配体-药物轭合物 |
WO2010132547A2 (en) * | 2009-05-12 | 2010-11-18 | Mallinckrodt Inc. | Oxaza heterocyclic compounds for phototherapy |
WO2010132554A2 (en) | 2009-05-12 | 2010-11-18 | Mallinckrodt Inc. | Diaza heterocyclic compounds for phototherapy |
US8731655B2 (en) | 2009-05-12 | 2014-05-20 | Mallinckrodt Llc | Compounds containing acyclic N-N bonds for phototherapy |
US8829020B2 (en) | 2009-07-16 | 2014-09-09 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
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US5518888A (en) * | 1993-10-26 | 1996-05-21 | Thomas Jefferson University | ST receptor binding compounds and methods of using the same |
US5605809A (en) * | 1994-10-28 | 1997-02-25 | Oncoimmunin, Inc. | Compositions for the detection of proteases in biological samples and methods of use thereof |
US6485704B1 (en) * | 2001-05-04 | 2002-11-26 | Mallinckrodt Inc. | Azo compound for type I pototherapy |
-
2002
- 2002-10-15 US US10/272,123 patent/US6747151B2/en not_active Expired - Fee Related
-
2003
- 2003-10-14 AU AU2003279973A patent/AU2003279973B2/en not_active Ceased
- 2003-10-14 WO PCT/US2003/032699 patent/WO2004035536A2/en active Application Filing
- 2003-10-14 EP EP03773279A patent/EP1551461A4/en not_active Withdrawn
- 2003-10-14 JP JP2004545327A patent/JP2006503096A/ja active Pending
- 2003-10-14 CA CA002502211A patent/CA2502211A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU2003279973A1 (en) | 2004-05-04 |
WO2004035536A2 (en) | 2004-04-29 |
US20030072763A1 (en) | 2003-04-17 |
WO2004035536A3 (en) | 2004-07-29 |
US6747151B2 (en) | 2004-06-08 |
EP1551461A4 (en) | 2007-08-01 |
CA2502211A1 (en) | 2004-04-29 |
EP1551461A2 (en) | 2005-07-13 |
AU2003279973B2 (en) | 2008-04-10 |
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