KR970061254A - 에스트로겐 길항제 및 에스트로겐 작용제에 의해 병리학적 증상을 억제하기 위한 조성물 - Google Patents

에스트로겐 길항제 및 에스트로겐 작용제에 의해 병리학적 증상을 억제하기 위한 조성물 Download PDF

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KR970061254A
KR970061254A KR1019970006288A KR19970006288A KR970061254A KR 970061254 A KR970061254 A KR 970061254A KR 1019970006288 A KR1019970006288 A KR 1019970006288A KR 19970006288 A KR19970006288 A KR 19970006288A KR 970061254 A KR970061254 A KR 970061254A
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composition
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phenyl
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independently selected
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데이비드 비 맥클리안
데이비드 디 톰슨
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스피겔 알렌 제이
화이자 인코포레이티드
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Priority to TW087112955A priority Critical patent/TW514681B/zh

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Abstract

본 발명은 에스트로겐 작용제에 반응하는 기관계에 관련된 병리학적 증상의 치료가 요구되는 포유동물에게 유효량의 하기 화학식 (1)의 화합물을 투여함을 포함하는, 상기 증상을 억제하는 신규한 방법 및 상기 증상을 억제하기 위한 조성물을 제공한다.

Description

에스트로겐 길항제 및 에스트로겐 작용제에 의해 병리학적 증상을 억제하기 위한 조성물
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (22)

  1. 유효량의 하기 화학식 (1)의 화합물 및 이의 광학적 및 기하학적 이성체; 및 이의 무독성의 약리학적으로 허용되는 산부가염, N-옥시드, 에스테르 및 4급 암모늄염을 약학적으로 허용되는 담체, 희석제 또는 부형제와 함께 포함하는, 자궁암, 아쥬반트성 유방암, 유방 장애, 남성 유방암, 편두통, 요실금, 질 위축, 방광염, 노인성 여성유방증, 당뇨병, 저혈당증, 상처 치유력 감소, 흑색종, 임포텐스, 염증성 위장 질환, 초과량의 타키키닌에 의한 CNS 및 GI 장애; 리비도의 감소; 면역계 장애, 임신율의 감소, 폐고혈압증, 여드름, 지루증, 자동면역 질환, 터너 중후군, 탈모증, 다모증, 초과량의 뉴로키닌과 관련된 장애, 및 흡연 및 알콜 남용을 포함하는 강박 장애로 구성된 그룹에서 선택되는 항안티에스트로겐 또는 에스트로겐 작용제에 의한 억제에 대해 민감하거나 부분적으로 민감한 병리학적 증상을 억제하는 조성물:
    상기 식에서, A는 CH2및 NR에서 선택되고; B, D 및 E는 독립적으로 CH 및 N으로부터 선택되고;Y는 (a) R4로부터 독립적으로 선택되는 1 내지 3개의 치환체에 의해 임의로 치환된 페닐; (b) R4로부터 독립적으로 선택되는 1 내지 3개의 치환체에 의해 임의로 치환된 나프틸, (c) R4로부터 독립적으로 선택되는 1 내지 2개의 치환체에 의해 임의로 치환된 C3-C8사이클로알킬; (d) R4로부터 독립적으로 선택되는 1 내지 2개의 치환체에 의해 임의로 치환된 C3-C8사이클로알케닐; (e) R4로부터 독립적으로 선택되는 1 내지 3개의 치환체에 의해 임의로 치환된, -O-, -NR2- 및 -S(O)n-으로 구성된 그룹에서 선택되는 두개 이하의 헤테로원자를 함유하는 5원 헤테로사이클; (f) R4로부터 독립적으로 선택되는 1 내지 3개의 치환체에 의해 임의로 치환된, -O-, -NR2- 및 -S(O)n-으로 구성된 그룹에서 선택되는 두개 이하의 헤테로원자를 함유하는 6원 헤테로사이클; 또는 (g) 페닐 환에 융합된 5 또는 6원의 헤테로사이클릭 환으로 구성되고, 이대 상기 헤테로사이클릭환은 R4로부터 독립적으로 선택되는 1 내지 3개의 치환체에 의해 임의로 치환된, -O-, -NR2- 및 -S(O)n-으로 구성된 그룹에서 선택되는 두개 이하의 헤테로원자를 함유하는 비사이클릭 환 시스템이고; Z1은 (a) -(CH2)pW(CH2)q-; (b) -O(CH2)pCR5R6-; (c) -O(CH2)pW(CH2)q-; (d) -OCHR2CHR3-; 또는 (e) -SCHR2CHR3-이고; G는 (a) -NR7R8;(b) 상기 식에서 n은 0, 1 또는 2이고; m은 1, 2 또는 3이고; Z2는 -NH-, -O-, -S- 또는 -CH2-이고; 임의로 하나 또는 두개의 페닐 환과 인접한 탄소원자상에 융합되고, 임의로 1 내지 3개의 치환체에 의해 탄소상에서 독립적으로 치환되고, 임의로 R4로부터 선택된 화학적으로 적합한 치환체로 질소상에서 독립적으로 치환되거나; 또는 (c) 가교화되거나 융합되고 임의로 R4로부터 독립적으로 선택된 1 내지 3개의 치환체에 의해 치환된, 5 내지 12개의 탄소원자를 함유하는비사이클릭 아민이거나; 또는 조합시 Z1및 G는일 수 있고; W는 (a) -CH2-; (b) -CH=CH-; (c) -O-; (d) -NR2-; (e) -S(O)n-; (f); (g) -CR2(OH)-; (h) -CONR2-; (i) -NR2CO-; (j); 또는 (k) -C≡C-이고; R은 수소 또는 C1-C6알킬이고; R2및 R3은 독립적으로 (a) 수소; 또는 (b) C1-C4알킬이고; R4는 (a) 수소; (b) 할로겐; (c) C1-C6알킬; (d) C1-C4알콕시; (e) C1-C4아실록시; (f) C1-C4알키티오; (g) C1-C4알킬설피닐; (h) C1-C4알킬설포닐; (i) 하이드록시(C1-C4)알킬; (j) 아릴(C1-C4)알킬; (k) -CO2H; (l) -CN; (m) -CONHOR; (n) -SO2NHR; (o) -NH2; (p) C1-C4알킬아미노; (q) C1-C4디알킬아미노;(r) -NHSO2R; (s) -NO2; (t) -아릴; 또는 (u) -OH이고; R5및 R6은 독립적으로 C1-C8알킬 또는 함께 C3-C10카보이사이클릭 환을 형성하고; R7및 R8은 독립적으로 (a) 페닐; (b) 포화되거나 불포화된 C3-C10카보사이클릭 환; (c) -O-, -N- 및 -S-로부터 선택된 두개까지의 헤테로원자를 함유하는 C3-C10헤테로사이클릭 환; (d) H; (e) C1-C6알킬; 또는 (f) R5또는 R6과 함께 3 내지 8원의 질소 함유 환을 형성하고; 선형 또는 환형의 R7및 R8은 C1-C6알킬, 할로겐, 알콕시, 하이드록시 및 카복시로부터 독립적으로 선택되는 3개까지의 치환체에 의해 임의로 치환될 수 있고; R7및 R8에 의한 환은 임의로 페닐 환에 융합될 수 있고; e는 0, 1 또는 2이고; m은 1, 2 또는 3이고; n은 0, 1 또는 2이고; p는 0, 1, 2 또는 3이고; q는 0, 1, 2 또는 3이다.
  2. 제1항에 있어서, 화학식 (1)의 화합물이 하기 구조의 화합물인 조성물:
    상기 식에서, G는
    이다.
  3. 제1항에 있어서, 화학식 (1)이 화합물이 시스-6-(4-플루오로-페닐)-5-[4-(2-피페리딘-1-일-에톡시)-페닐]-5,6,7,8-테트라하이드로나프탈렌-2-올; (-)-시스-6-페닐-5-[4-(2-피롤리딘-1-일-에톡시)-페닐]-5,6,7,8-테트라하이드로나프탈렌-2-올; 시스-6-페닐-5-[4-(2-피롤리딘-1-일-에톡시)-페닐]-5,6,7,8-테트라하이드로나프탈렌-2-올; 시스-1-[6'-피롤로디노에톡시-3'-피리딜]-2-페닐-6-하이드록시-1,2,3,4-테트라하이드로나프탈렌; 1-(4'-피롤리디노에톡시페닐)-2-(4-플루오로페닐)-6-하이드록시-1,2,3,4-테트라하이드로이소퀴놀린; 시스-6-(4-하이드록시페닐)-5-[4-(2-피페리딘-1-일-에톡시)-페닐]-5,6,7,8-테트라하이드로나프탈렌-2-을; 및 1-(4'-피를리디놀에톡시페닐)-2-페닐-6-하이드록시-1,2,3,4-테트라하이드로이소퀴놀린으로 구성된 그룹에서 선택되는 조성물.
  4. 제1항에 있어서, 상기 병리학적 증상이 유방 장애인 조성물.
  5. 제1항에 있어서, 상기 병리학적 증상이 질 위축인 조성물.
  6. 제1항에 있어서, 상기 병리학적 증상이 발광 감염인 조성물.
  7. 제1항에 있어서, 상기 병리학적 증상이 노인성 여성화유방증인 조성물.
  8. 제1항에 있어서, 상기 병리학적 증상이 당뇨병인 조성물.
  9. 제1항에 있어서, 상기 병리학적 증상이 과혈당증인 조성물.
  10. 제1항에 있어서, 상기 병리학적 증상이 상처 치유력 불능인 조성물
  11. 제1항에 있어서, 상기 병리학적 증상이 리비도의 감소인 조성물.
  12. 제1항에 있어서, 상기 병리학적 증상이 면역계 장애인 조성물.
  13. 제1항에 있어서, 상기 병리학적 증상이 임신 감소인 조성물.
  14. 제1항에 있어서, 상기 병리학적 증상이 폐 고혈압 질환인 조성물.
  15. 제1항에 있어서, 상기 병리학적 증상이 여드름인 조성물.
  16. 제1항에 있어서, 상기 병리학적 증상이 지루증 조성물.
  17. 제1항에 있어서, 상기 병리학적 증상이 자기면역 질환인 조성물.
  18. 제1항에 있어서, 상기 병리학적 증상이 트너 증후군인 조성물.
  19. 제1항에 있어서, 상기 병리학적 증상이 다모증인 조성물.
  20. 제1항에 있어서, 상기 병리학적 증상이 탈모증인 조성물.
  21. 제1항에 있어서, 상기 병리학적 증상이 강박 장애인 조성물.
  22. 제1항에 있어서, 상기 병리학적 증상이 원하지 않는 임신인 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019970006288A 1996-02-28 1997-02-27 에스트로겐 길항제 및 에스트로겐 작용제에 의해 병리학적 증상을 억제하기 위한 조성물 KR970061254A (ko)

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US20040009994A1 (en) 2004-01-15
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