KR950000875A - 골다공증 치료제의 탐색 물질 및 탐색방법 - Google Patents

골다공증 치료제의 탐색 물질 및 탐색방법 Download PDF

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KR950000875A
KR950000875A KR1019940013849A KR19940013849A KR950000875A KR 950000875 A KR950000875 A KR 950000875A KR 1019940013849 A KR1019940013849 A KR 1019940013849A KR 19940013849 A KR19940013849 A KR 19940013849A KR 950000875 A KR950000875 A KR 950000875A
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alkoxy
compound
estrogen
transcription
response element
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노라 양 나
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피터 지. 스트링거
일라이 릴리 앤드 캄파니
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Abstract

본 발명은 골다공증 치료제 및 혈청 지질 강하제의 탐색방법에 관한 것이다. 본 발명은 "랄록시펜 반응 요소"로 나타내는 신규한 조절 요소를 포함하는 포유동물 형질전환 성장 인자 β유전자의 프로모터 영역으로부터의 핵산의 단리, 클로닝 및 사용방법에 관한 것이다. 본 발명은 또한 상기 랄록시펜 반응 요소가 리포터 유전자의 전사를 조절하도록 상기 리포터 유전자에 작동적으로 결합된 상기 요소를 함유하는 진핵 세포를 포함한다. 본 발명은 기존의 골다공증 치료 섭생과 관련된 유해하거나 바람직하지 못한 부작용이 없는, 상기와 같은 랄록시펜 반응 요소에 작동적으로 결합된 유전자의 전사를 유도하는 골다공증 치료제의 탐색방법을 제공한다.

Description

골다공증 치료제의 탐색 물질 및 탐색방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 TGFβ-1 유전자의 프로모터 영역을 도시한다. 제2도는 TGFβ-2 유전자의 프로모터 영역을 도시한다. 제3도는 TGFβ-3 유전자의 프로모터 영역을 도시한다.

Claims (6)

  1. TGFβ 유전자(여기에서 인간 TGFβ 유전자는 TGFβ-2 또는 TGFβ-3이다)의 프로모터 영역으로부터 단리된 랄록시펜(raloxifene) 반응 요소를 포함하는 핵산.
  2. (a) 포유동물 프로모터의 랄록시펜 반응 요소로부터 전사를 유도하는 화합물의 능력을 분석하는 단계; (b) 랄록시펜 반응 요소를 갖지 않는 포유동물 프로모터로부터 전사를 유도할 수 없는 화합물을 분석하는 단계; (c) 에스트로겐 반응성 프로모터로부터 전사를 유도할 수 없는 화합물을 분석하는 단계; 및 (d) 에스트로겐의 존재하에서 에스트로겐 반응성 프로모터로부터의 에스트로겐-유도된 전사를 억제하는 화합물의 능력을 분석하는 단계를 포함하고, 포유동물 프로모터의 랄록시펜 반응 요소로부터 전사를 유도할 수 있고, 비-특이적인 전사 유도물질은 아니며, 포유동물 프로모터의 에스트로겐 반응 요소로부터 전사를 유도할 수 없고, 항에스트로겐 또는 비에스트로겐 화합물인 다수의 화합물을 확인함을 포함하는 골다공증 치료제로서의 가능성을 갖는 화합물을 확인하기 위한 다수 화합물의 탐색방법.
  3. 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 포유동물에게 투여함을 포함하는 상기 포유동물의 골형성 유도 방법;
    (Ⅰ)
    상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
  4. 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 투여함을 포함하는 골다공증의 치료 방법;
    (Ⅰ)
    상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
  5. 에스트로겐 수용체에 결합시, TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 투여함을 포함하는 골균열의 치료 방법;
    (Ⅰ)
    상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
  6. (a) TGFβ-3 유전자의 프로모터 영역의 랄록시펜 반응 요소로부터 전사를 강력하게 유도하고; (b) 랄록시펜 반응 요소를 갖지 않는 포유동물 프로모터로부터는 전사를 유도하지 않으며; (c) 에스트로겐 반응성 프로모터로부터 전사를 유도하지 않고; (d) 에스트로겐의 존재하에서 에스트로겐 반응성 프로모터로부터의 에스트로겐 유도된 전사를 억제하는 화합물(단, 상기 화합물은 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염이외의 화합물이다)을 포유동물에게 투여함을 포함하는 상기 포유동물의 골형성 유도 방법;
    (Ⅰ)
    상기식에서, n은 0,1 또는 2이고; R 및 R1은 독립적으로 수소, 하이드록실, C1-C6-알콕시, C1-C6-아실록시, C1-C6-알콕시-C2-C6-아실록시, R3-치환된 아릴록시, R3-치환된 아로일록시, R4-치환된 카보닐록시, 클로로 또는 브로모이고; R2는 피롤리디노, 피페리디노 또는 헥사메틸렌이미노로 이루어진 그룹중에서 선택된 헤테로사이클릭 고리이고; R3는 C1-C3-알킬, C1-C3-알콕시, 수소 또는 할로이고; R4는 C1-C6-알콕시 또는 아릴록시이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019940013849A 1993-06-21 1994-06-20 골다공증 치료제의 탐색 물질 및 탐색방법 KR950000875A (ko)

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