KR970701193A - 작용화가 개선된 텍사피린 금속 착물(Texaphyrin metal complexes having improved functionalization) - Google Patents

작용화가 개선된 텍사피린 금속 착물(Texaphyrin metal complexes having improved functionalization)

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KR970701193A
KR970701193A KR1019960704419A KR19960704419A KR970701193A KR 970701193 A KR970701193 A KR 970701193A KR 1019960704419 A KR1019960704419 A KR 1019960704419A KR 19960704419 A KR19960704419 A KR 19960704419A KR 970701193 A KR970701193 A KR 970701193A
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iii
hydrogen
texaphyrin
oxyalkyl
hormones
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죠나단 엘. 세쓸러
타랙 디. 모디
그레고리 더블류. 헴미
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패러비 레이
보드 오브 리젠츠, 더 유니버시티 오브 텍사스 시스템
스튜어 마크
파마사이클릭스, 인코포레이티드
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Abstract

작용화가 개선된 화학식(1)의 텍사피린 금속 착물은 거대환의 2, 7, 12, 15, 18 및/또는 21 위치에 전자 공여 그룹의 첨가 및/또는 15 또는 18 위치에 전자 제거 그룹의 첨가를 포함한다. 2, 7, 12, 15, 18 및/또는 21 위치에서 전자 공여 그룹은 거대환의 방향족 π 시스템에 전자를 공급하여 금속 착물의 비금속화외 이민 결합의 가수분해를 안정화시킨다. 안정성이 개선된 텍사피린 금속착물은 국재화, 자기공명상, 방사선감작화, 방사선 치료요법, 형광성 영상화, 광역학적 종양 치료요법 및 세포특성을 위해 단일선 산소생성이 요구되는 적용에 유용하다. 15 또는 18 위치에서 전자 제거 그룹은 거대환이 더욱 쉽게 환원되도록 하는데, 예를들면 산화환원 포텐셜이 낮아질수록 거대분자는 더욱 용이하게 전자를 수득하여 라디칼을 형성한다. 이와같이 산화 환원 포텐셜이 낮은 텍사피린이 방사선감작화 적용시 유용하다.

Description

작용화가 개선된 텍사피린 금속 착물(Texaphyrin metal complexes having improved functionalization)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (17)

  1. 화학식 (1)의 텍사피린.
    상기 식에서, M은 H; Ca(Ⅱ), Mn(Ⅱ), Co(Ⅱ), Ni(Ⅱ), Zn(Ⅱ), Cd(Ⅱ), Hg(Ⅱ), Fe(Ⅱ), Sm(Ⅱ) 및 UO2(Ⅱ)로 이루어진 그룹 중에서 선택된 2가 금속 양이온 또는 Mn(Ⅲ), Co(Ⅲ), Ni(Ⅲ), Fe(Ⅲ), Ho(Ⅲ), Ce(Ⅲ), Y(Ⅲ), In(Ⅲ), Pr(Ⅲ), Nd(Ⅲ), Sm(Ⅲ), Eu(Ⅲ), Gd(Ⅲ), Tb(Ⅲ), Dy(Ⅲ), Er(Ⅲ), Tm(Ⅲ), Yb(Ⅲ), Lu(Ⅲ), La(Ⅲ) 및 U(Ⅲ)로 이루어진 그룹 중에서 선택된 3가 금속 양이온이고; R1내지 R4, R7및 R8은 독립적으로 수소, 할라이드, 하이드록실, 알킬, 아릴, 할로알킬, 니트로, 포르밀, 아실, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 사카라이드, 카복시, 카복시알킬, 카복시아미드알킬, 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드, 사프피린 분자, 또는 올리고뉴클레오타이드, 항체 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플이며; R6및 R9는 독립적으로 R1내지 R4, R7및 R8의 그룹성 중에서 선택되고, 단 할라이드는 요오다이드 이외의 것이고 할로알킬은 요오도알킬 이외의 것이며; R5및 R10내지 R12는 독립적으로 수소, 알킬, 아릴, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 카복시알킬, 카복시아미드알킬, 또는 사카라이드, 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플이고; 하나 이상의 R5, R6, R10, R11및 R12는 수소 이외의 것이며; n은 5 이하의 정수이다.
  2. 제1항에 있어서, R1내지 R4및 R6내지 R9가 독립적으로 수소, 하이드록실, 알킬, 아릴, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 사카라이드, 카복시알킬, 카복시아미드알킬, 올리고클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드, 사프피린 분자, 또는 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플이고; R5및 R10내지 R12가 독립적으로 수소, 알킬, 아릴, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 카복시알킬, 카복시아미드알킬, 또는 사카라이드, 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플린 텍사피린.
  3. 제1항에 있어서, R1내지 R4, R7및 R8이 독립적으로 수소, 할라이드, 하이드록실, 알킬, 아릴, 할로알킬, 니트로, 포르밀, 아실, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 사카라이드, 카복시, 카복시알킬, 카복시아미드알킬, 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드, 사프피린 분자, 또는 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플이고; R5및 R10내지 R12가 독립적으로 수소, 알킬, 아릴, 하이드록시알킬, 옥시알킬, 옥시하이드록시알킬, 카복시알킬, 카복시아미드알킬, 또는 사카라이드, 올리고뉴클레오타이드, 항체, 호르몬, 생물학적 수용체에 대해 친화성이 있는 펩타이드 또는 사프피린 분자에 대한 커플이며; R6및 R9가 독립적으로 요오다이드 이외의 할라이드, 토르밀, 아실, 카복시 또는 니트로인 텍사피린.
  4. 제1항 내지 제3항 중의 어느 한 항에 있어서, 커플이 아미드, 티올, 티오에테르 또는 에테르 공유 결합인 텍사피린.
  5. 제1항 내지 제3항 중의 어느 한 항에 있어서, 올리고뉴클레오타이드. 항체, 호르몬 또는 사프피린이 치료부위에 국재화하기 위한 결합 특이성을 지니는 텍사피린.
  6. 제1항 내지 제3항 중의 어느 한 항에 있어서, 생물학적 수용체가 치료부위에 국재화되는 텍사피린.
  7. 제1항에 있어서, 하나 이상의 R5및 R10내지 R12가 수소 이외의 것이고; R5가 수소 이외의 것인 경우 R6이 수소, 불소 또는 하이드록실이며; R10이 수소 이외의 것인 경우, R9가 수소, 불소 또는 하이드록실인 텍사피린.
  8. 제1항에 있어서, 하나 이상의 R6및 R9가 수소 이외의 것이고; R6이 수소 이외의 것인 경우. R5가 수소 또는 메틸이며; R9가 수소 이외의 것인 경우, R10이 수소 또는 메틸인 텍사피린.
  9. 제1항 내지 제3항 또는 제7항 중의 어느 한 항에 있어서, R5와 R10이 수소, 니트로, 카복시, 설폰산, 하이드록시, 옥시알킬 또는 할라이드인 치환체 R13을 지니는 아릴인 텍사피린.
  10. 제1항에 있어서, 각각의 R1내지 R12가 표1 및 표2에 설정된 R1내지 R12에 대한 치환체 중의 어느 하나인 텍사피린.
  11. 제1항에 있어서, R1이 CH2(CH2)2OH이고; R2및 R|3이 CH2CH3이며; R4, R5및 R10이 CH3이고; R6및 R9가 H이며; R7및 R8이 0(CH|2CH2O)3CH3인 텍사피린.
  12. 제11항에 있어서, R11및 R12가 H 또는 CH3인 텍사피린.
  13. 표1 또는 표2의 텍사피린 A1 내지 A56 중에서 선택되는 텍사피린.
  14. 제1항 내지 제3항, 제10항 및 제13항 중의 어느 한 항에 있어서, 금속이 Lu(Ⅲ), La(Ⅲ), In(Ⅲ), Gd(Ⅲ), Eu(Ⅲ), 또는 Dy(Ⅲ)인 텍사피린.
  15. 광역학적 제제로서 사용하기 위한 약제학적 조성물의 제조시 제1항, 제10항 및 제13항 중의 어느 한 항에 따르는 텍사피린의 용도.
  16. 자기 공명 영상 제제로서 사용하기 위한 약제학적 조성물의 제조시 제1항, 제10항 및 제13항 중의 어느 한 항에 따르는 텍사피린의 용도.
  17. 방사선 감작제로서 사용하기 위한 약제학적 조성물의 제조시 제1항, 제10항 및 제13항 중의 어느 한 항에 따르는 텍사피린의 용도
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019960704419A 1994-02-15 1995-02-15 작용화가 개선된 텍사피린 금속 착물(Texaphyrin metal complexes having improved functionalization) KR970701193A (ko)

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