KR960003726A - 골손실의 억제를 위한 복합 치료 - Google Patents

골손실의 억제를 위한 복합 치료 Download PDF

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KR960003726A
KR960003726A KR1019950021267A KR19950021267A KR960003726A KR 960003726 A KR960003726 A KR 960003726A KR 1019950021267 A KR1019950021267 A KR 1019950021267A KR 19950021267 A KR19950021267 A KR 19950021267A KR 960003726 A KR960003726 A KR 960003726A
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존 블랙 래리
죠셉 쿨리난 죠오지
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피터 지, 스트링거
일라이 릴리 앤드 캄파니
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Abstract

본 발명은 골손실의 억제가 필요한 인간에게 1) 트리아릴에틸렌; 2) 2,3－디아릴－2H－1－벤조피란; 3) 1－아미노알킬－2－페닐인돌; 4) 2－페닐－3－아로일벤조티오펜; 5) 1－치환된－2－아릴－디하이드로나프탈렌 및 6) 벤조푸란중에서 선택된 1군 화합물; 및 비스포스포네이트인 2군 화합물, 또는 이들의 약학적으로 허용가능한 염 및 용매화물을 투여함을 포함하는 골손실의 신규한 억제 방법을 제공한다. 또한 약학 조성물 및 염의 복합물도 포함한다.

Description

골손실의 억제를 위한 복합 치료
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Claims (12)

  1. 골손실의 억제를 위한, 1) 트리아릴에틸렌; 2) 2,3－디아릴－2H－1－벤조피란; 3) 1－아미노알킬－2－페닐인돌; 4) 2－페닐－3－아로일벤조티오펜; 5) 1－치환된－2－아릴－디하이드로나프탈렌 및 6) 벤조푸란중에서 선택된 1군 화합물; 및 비스포스포네이트인 2군 화합물, 또는 이들의 약학적으로 허용가능한 염 및 용매화물.
  2. 제1항에 있어서, 상기 비스포스포네이트가 알렌드로네이트, 포미드로네이트, 리제드로네이트, 사이클로헵틸 아미노 메틸리덴 비스포스포네이드, 및 3－피롤리도닐－1－하이드록시 프로필리덴 비스포스포네이트중에서 선택된 화합물.
  3. 제1항에 있어서, 하기 일반식(Ⅰ),(Ⅱ) 또는 (Ⅲ)의 트리아릴에틸렌인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물 :
    상기식들에서, R은 일반식 －OCnH2nA의 염기성 에테르 그룹이며, 여기에서 n은 2,3 또는 4이고, 디알킬아미노 그룹(이때 상기 알킬 그룹은 탄소수 1 내지 4를 갖는다), 또는 N－피페리디닐, N－피롤리디닐, N－모르폴리닐 및 N－헥사메틸렌이미노 그룹중에서 선택된 환상 구조이고; R1은 각각 독립적으로 수소, 하이드록시, 할로겐, 메톡시이고; X는 할로겐이고; R2및 A3는 독립적으로 수소 및 메틸중에서 선택되고; R4는 이소프로필, 이소프로펜－2－일, 또는 모노 또는 디하이드록시 이소프로필이고; R5는 하이드록시 또는 포스페이트(－OPO3H2)이다.
  4. 제1항에 있어서, 2,3－디아릴－2H－1－벤조피란인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물.
  5. 제4항에 있어서, 상기 2,3－디아릴－2H－1－벤조피란인 하기 일반시기(Ⅳ)를 갖는 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물:
    상기식에서, R6및 R7은 동일하거나 상이하게 수소, 하이드록시, C1－C17알콕시 또는 C2－C18알콕시카보닐이고; R8은 －OCH2CH2N또는 OCH2CH2N이다.
  6. 제1항에 있어서, 하기 일반식(Ⅴ)의 1－아미노알킬－2－페닐인돌인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물:
    상기식에서, R9는 수소 또는 메틸이고; R10및 R11은 메톡시 또는 하이드록시이고; m은 4 내지 8이고; Y는 NR12R15이고, 여기에서 R12및 R13은 독립적으로 수소, 메틸 및 에틸중에서 선택되거나, 또는 R12및 R13중의 하나는 수소이고 다른 하나는 벤질이거나, 또는 R12및 R13은 질소원자의 결합하여 피롤리디닐, 피페리디닐 또는 모르폴리닐 그룹을 형성한다.
  7. 제1항에 있어서, 하기 일반식(Ⅵ)의 2－페닐－3－아로일벤조〔b〕티오펜인 1군 화합물 및 그의 약학적으로 허용가능한 산 부가염 및 용매화물:
    상기식에서, R16은 수소, 하이드록시, C1－C5알콕시, C1－C7알카노일옥시, C3－C7사이클로알카노일옥시, (C1－C6알콕시)－C1－C7알카노일옥시, 치환되거나 비치환된 아로일옥시 또는 치환되거나 비치환된 아릴옥시카보닐옥시이고; R17은 수소, 하이드록시, C1－C5알콕시, 아다만토일옥시, 클로로, 브로모, C1－C7알카노일옥시, C3－C7사이클로알카노일옥시, (C1－C6알콕시)－C1－C7알카노일옥시, 치환되거나 비치환된 아로일옥시 또는 치환되거나 비치환된 아릴옥시카보닐옥시이고; R18은 O－CH2－CH2－X´－NR19R20이고, 여기에서 X´는 단일결합 또는 －CH2－이고, R19및 R20은 독립적으로 C1－C4알킬이거나 또는 이들이 결합된 질소원자와 함께 피롤리디닐, 피폐리디닐, 헥사메틸렌이미닐 또는 모르폴리닐 고리를 형성한다.
  8. 제7항에 있어서, 상기 2－페닐－3－아로일벤조〔b〕티오펜이 〔6－하이드록시－2－(4－하이드록시페닐)벤조〔b〕티엔－3－일〕〔4－〔2－(1－피페리디닐)에톡시〕페닐〕메타논인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물.
  9. 제7항에 있어서, 상기 2－페닐－3－아로일벤조〔b〕티오펜이 〔6－하이드록시－2－(4－하이드록시페닐)벤조〔b〕티엔－3－일〕〔4－〔2－(1－피롤리디닐)에톡시〕페닐〕메타논인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물.
  10. 제1항에 있어서, 하기 일반식(Ⅶ) 또는 (Ⅷ)의 1－치환된－2－아릴－디하이드로나프탈렌인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물:
    상기식들에서, Z는 －CH2－CH2－ 또는 －CH=CH－이고; R16은 수소, 하이드록시 또는 C1－C5알콕시이고; R17은 수소, 하이드록시, C1－C5알콕시, C1－C5아실옥시, C1－C5알콕시카보닐옥시, 벤질옥시, 아다만토일옥시, 클로로 또는 브로모이고; R18은 C1－C5알콕시 또는 O－CH2－CH2－NR19R20이고, 여기에서 R19및 R20은 독립적으로 C1－C4알킬이거나, 또는 이들이 결합된 질소원자와 함께 피롤리디닐, 피페리디닐, 헥사메틸렌이미닐 또는 모르폴리닐 고리를 형성하나; 단 R17이 수소일때, R16은 수소, 하이드록시 또는 C1－C5알콕시이고, R16및 R17중 적어도 하나는 수소가 아니며; R19및 R20은 C1－C8알킬이거나, 또는 이들이 결합된 질소원자와 함께 피롤리디닐, 2－메틸피롤리디닐, 2,2－디메틸피롤리디닐, 피페라지닐, 4－메틸피페라지닐, 2,4－디메틸피페라지닐, 모르폴리닐, 피페리디닐, 2－메틸피페리디닐, 3－메틸피페리디닐, 헥사메틸렌이미닐, 호모피페라지닐 및 호모모르폴리닐중에서 선택된 5 내지 7원의 포화된 헤테로사이클릭 라디칼을 형성하고; q는 2 내지 6이고; p는 1 내지 4이고; R21은 C1－C8알콕시이다.
  11. 제1항에 있어서, 하기 일반식(Ⅸ)의 2－치환된－3－아릴－벤조푸란인 1군 화합물 및 그의 약학적으로 허용가능한 염 및 용매화물 :
    상기식에서, X2는 할로이고; Y2는 단일결합 또는 －CH2－이고; R22는 수소 또는 메틸이고; R23은 －NR19R20그룹이고, 여기에서 R19및 R20은 독립적으로 C1－C4알킬이거나 또는 이들이 결합된 질소원자와 함께 피롤리디닐, 피페리디닐, 헥사메틸렌이미닐 또는 모르폴리닐 고리를 형성한다.
  12. 제1항 내지 11항중 어느 한 항에 정의된 1군 및 2군 화합물을 포함하는, 인간의 골손실 억제에 사용하기 위한 약학 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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