KR910006325A - 아미노산 유도체 - Google Patents

아미노산 유도체 Download PDF

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KR910006325A
KR910006325A KR1019900014801A KR900014801A KR910006325A KR 910006325 A KR910006325 A KR 910006325A KR 1019900014801 A KR1019900014801 A KR 1019900014801A KR 900014801 A KR900014801 A KR 900014801A KR 910006325 A KR910006325 A KR 910006325A
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유라스지크 호르스트
라다쯔 페터
좀브로에크 요하네스
클라우스오트.슈미트게스
민크 클라우스-오토
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위르겐 호이만, 쉬틀러
메르크 파텐트 게젤샤프트 미트 베슈랭크터 하르퉁
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Abstract

내용 없음

Description

아미노산 유도체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (7)

  1. 다음 일반식 (Ⅰ)의 신규한 아미노산 유도체 및 이의 염.
    상기식에서, R1은R6R7N-,R6-NH-C(=NH)-NH-,NC-NH-C(=NH)-NH-,R6OOC-,R6O3S-또는 R6-O-(CH2CH2O),-이고, Z는-O-, -CH2-, -CH=CH-, -C=C-, -NH8-, -CH2-O-, CH2-NR8- 또는-CH2-S-이고, E는 펩타이드 형식으로 함께 결합하고, Abu, Ala, Cal, His, Ile, Leu, Met, Nle, Nva, Phe, Trp, Tyr과 Val의 군중에서 선택된 0 내지 2개의 아미노산 잔기이고, Q는 0 또는 NR10이고, Y는 -C1H2-R11, -C1H2-R12또는 -CW-H2W-(CR13)S-C1H2-R11이고, WR3는-OR3또는 -NHR3이고, R2, R3및 R11은 각기 H, A, Ar, Ar-알킬, Het, Het-알킬, 또한 비치환되거나, A,AO 및/또는 Hal로 한번 또는 여러번 치환된 탄소수 3 내지 7의 시클로알킬, 탄소수 4 내지 11의 시클로알킬알킬, 각기 탄소수 7내지 14의 비시클로알킬, 또는 트리시클로알킬, 또는 각기 탄소수 8 내지 18의 비시클로알킬알킬 또는 트리시클로알킬알킬이고, R4및 R13은 각각 (H, OH), (H, NH2) 또는 =O이고, R5,R6및 R10은 각각 H 또는 A이고, R6및 R7은 각각 H, A 또는 Ar-알킬이고, R7은 또한 R9-O-CXH2X-CO-, R9-CXH2X-O-CO- 또는 Ac이고, R9은 A또는 Ar-알킬이고, R6R7N은 또한 비치환되거나,A, OH, NH2,NHA, NA2,NHAc, NH-CO-CXH2X-O-R9,NH-CO-O-CXH2X-R9, NH-SO2-A, 히드록시알킬, COOH, COOA, CONH2,CN, 아미노알킬, HAN-알킬,A2N-알킬,알킬, NH-CO-NH2,NH-CO-NHA, NH-CO-NA2,구아니딘일 또는 구아니딘일-알킬로 치환된 피롤리딘일, 피페리딘일, 모르폴린일 또는 피레라진일이고, R12는 -SO3H, -SO2NH2, -SO2NHA, -SO2NA2, -NH2, -NHA, -NA2, -NH-C(=NH)-NH2, -NH-C(=NH)-NHCN, -NH-CO-NH2, -NH-CO-NHA, -NH-CO-NA2, -NH-CS-NH2, -NH-CS-NHA, -NH-CS-NA2, -COOH, -COOA, -COO-알킬-Ar, -CONH2, -CONHA 또는 -CONA2이고, q는 0 또는 1이고, n은 0,1또는 2이고, s는 1 또는 2이고, m,p,t,w 및 x는 각기 0,1,2,3,4,5,6,7,8,9 또는 10이고, r은 1,2 또는 3이고, Ar은 비치환되거나 또는 A, OA, Hal, CF3, OH, NO2, 히드록시알킬, NH2, NHA, NA2, NHAc, SA, SO-A, SO2,-A, SO2NH2, SO2NHA, COOH, COOA, CONH2, CN, 아미노알킬, HAN-알킬, A2N-알킬, A2N-알킬,알킬및/또는 구아니딘일-알킬로 한번 또는 여러번 치환된 페닐이거나, 비치환된 나프틸이고, Het는 1 내지 4개의 N, O 및/또는 S원자를 갖고, 벤젠환과 융합되고/되거나, A, OA, Hal, CF3, OH, NO2, 카보닐산소, NH2, NHA, NA2, NHAc, SA, SO-A, SO2,-A, SO2NH2, SO2NHA, COOH, COOA, CONH2, CN, NH-SO2-A, Ar-알킬, Ar-알케닐, 히드록시알킬 및/또는 아미노알킬로 한번이상 치환될 수도 있는 포화 또는 불포화 5- 또는 6-원 헤테로시클릭 래디칼이고/이거나 그의 N 및/또는 S 헤테로 원자는 산화될 수 있고, Hal은 F, Cl, Br 또는 I이고 , Ac는 H-CO-,-A-CO-, CF3-CO-, Ar-알킬-CO- 또는 A-NH-CO이고,은 음이온이고, 대신에 일반식(I)의 화합물에 함유된 카복실 그룹이 카복실레이트 음이온의 형태인 경우, 부재할 수도 있고, -알킬-은 탄소수 1 내지 8의 알킬렌 그룹이고, A는 탄소수 내지 8의 알킬이고, 그리고 하나이상의 -NH-CO- 그룹은 하나이상의 -NA-CO-그룹으로 치환될 수도 있다.
  2. a)6-(BOC-아미노)-헥산오일-Phe-Isoser-AHCP-Ile AMPA, b)6-아미노-헥산오일-Phe-Isoser-AHCP-Ile ADPA, c)4-디메틸아미노-부티릴-Phe-Isoser-AHCP-Ile AMPA, d)4-아미노피페리디노카보닐-Phe-Isoser-AHCP-Ile ADPA, e)6-메톡시카보닐-헥산오일-Phe-Isoser-AHCP-Ile ADPA, f)6-카복시-헥산오일-Phe-Isoser-AHCP-Ile ADPA.
  3. 일반식(I)의 아미노산 유도체 및 이의 염을 제조하는 방법에 있어서, 그의 작용성 유도체중 하나로부터 가용매 분해제 또는 가수소분해제로 처리하여 유리시키거나, 또는 다음 일반식(Ⅱ)의 카복실산 또는 이의 반응성 유도체중 하나를 다음 일반식(Ⅲ)의 아미노 화합물과 반응시키고, 필요시 일반식(I)의 화합물중 기능적으로 변형된 아미노 및/또는 히드록실 그룹을 가용매분해제 또는 가수소분해제로 처리하여 유리시키고/시키거나, R4=(H,OH)또는 (H,NH2)인 일반식(I)의 화합물을 제조하기 위해 R4=θ인 일반식(I)의 아미노케토산 유도체를 환원시키거나 또는 환원적 아미노화하고/하거나, 라디칼 R1을 다른 라디칼 R1으로 전환하고/하거나, 일반식(I)의 화합물을 산으로 처리하여 이의 염중 하나로 전환시킴을 특징으로 하는 제조방법.
    상기식에서, G1은 (a)부재, (b)-NH-CHR2-CO-, (c)-NH-CHR2-CO-Z-CmH2m-CHWR3-CO-,(d)-NH-CHR2-CO-Z-CmH2m-CHWR3-CO-K-, (e)-NH-CHR2-CO-Z-CmH2m-CHWR3-CO-K-E1-,(f)-NH-CHR2-CO-Z-CmH2m-CHWR3-CO-K-E-, K는 -NH-CHR3-CR4-(CHR5)6-CO-이고, G2는 (a)-NH-CHR2-CO-Z-CmH2m-CHWR3-CO-K-E-Q-Y, (b)-Z-CmH2m-CHWR3-CO-K-E-Q-Y, (c)-K-E-Q-Y, (d)-E-Q-Y, (f)-NR10-Y 이고, E1+E2은 함꼐 E이다.
  4. 일반식(I)의 화합물 및/또는 이의 생리학적으로 허용가능한 염중 하나를 적어도 고체, 액체 또는 반-액체부형제 또는 조제와 함께, 필요시 하나 이상의 다른 활성물질(들)과 함께 적절한 투여형으로 전환시킴을 특징으로 하는 약제학적 제형의 제조방법.
  5. 적어도 하나의 일반식(I)의 화합물 및/또는 이의 생리학적으로 허용가능한 염중 하나를 함유하는 것을 특징으로 하는 약제학적 제형.
  6. 약물을 제조하기 위한 일반식(I)의 화합물 또는 이의 생리학적으로 허용가능한 염의 용도.
  7. 레닌-의존성 고혈압 꼬는 과알도스테론증을 치료하기 위한 일반식(I)의 화합물 또는 이의 생리학적으로 허용가능한 염의 용도.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019900014801A 1989-09-22 1990-09-19 아미노산 유도체 KR910006325A (ko)

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