KR890012650A - 5-리폭시게나제 억제성 4-(4-페닐-1-피페라지닐)페닐유도체 - Google Patents

5-리폭시게나제 억제성 4-(4-페닐-1-피페라지닐)페닐유도체 Download PDF

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KR890012650A
KR890012650A KR1019890002435A KR890002435A KR890012650A KR 890012650 A KR890012650 A KR 890012650A KR 1019890002435 A KR1019890002435 A KR 1019890002435A KR 890002435 A KR890002435 A KR 890002435A KR 890012650 A KR890012650 A KR 890012650A
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alkyl
hydrogen
cycloalkyl
substituted
aryl
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피에르 프란스 반 와우웨 제인
헤르스 쟌
야고브스 죠제프 박크스 레오
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구스타프 반 리이트
쟈안센 파아마슈우티카 엔.부이.
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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Abstract

내용 없음.

Description

5-리폭시게나제 억제성 4-(4-페닐-1-피페라지닐)페닐유도체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (10)

  1. 일반식(I)의 화합물, 그 산부가염 또는 그 입체이성체를 유효성분으로 효과량 함유하고 담체를 조성성분으로 하는 5-리폭시게나제 억제성 약제조성물.
    위의 일반식에서, R1및 R2는 각각 수소, C1-6알킬 또는 할로이고, R3및 R4는 각각 수소, 할로, 아미노, 니트로 또는 트리플루오로메틸이고, Y는 수소, 니트로, 아미노, 모노 또는 디(C1-6알킬)아미노, C1-6알킬 카르보닐아미노, C1-6알킬, C1-6알킬카르보닐, 히드록시, 할로, 모노 또는 디(C1-6알킬) 아미노설포닐 또는다음식의 복소환기이고,
    X는 O 또는 S이고, R5및 R6은 각각 C1-6알킬, C3-6알케닐, C3-6알키닐, 아릴, (아릴)C1-6알킬, C3-7시클로알킬 (C3-7시클로알킬)C1-6알킬, C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로 C1-6알킬인데, 위의 C1-6알킬, C3-7시클로알킬, (C3-7시클로알킬)C1-6알킬 및 (아릴) C1-6알킬은 C1-6알킬 또는 C3-7시클로알킬 부위의 탄소원자에서 옥소 또는 히드록시로 치환될 수 있으며, 단 상기 탄소원자는 R5또는 R6와 결합한 질소원자에 인접하여 있지 않고, R6은 수소일 수 있으며, A는 -C(R7)(R8)-이고, B는 -CH2-또는-CH2-CH2-이거나, A는 B와 함께 -CH=CH-(1) 또는 -CH=N-(m)의 2가기를 형성하고, 이들 기의 탄소원자는 X와 결합하고, R5또는 R6는 각각 수소 또는 C1-6알킬이기나, R7은 C1-6알킬옥시이고, -B-, -CH=CH-(1) 및 -CH=N(m)중의 1 또는 2의 수소원자는 C1-6알킬 또는 아릴로 치환될 수 있고, B기중에서 한쌍의 수소원자는, 1 또는 2의 C1-6알킬로 치환될 수 있는, C4-6알칸디일로 치환될 수 있고, D1은 -N=또는 -CH-이고, D2는-N=, =CH-또는 =CH-C(=0)-이고, E1은 -CH2-,-CH2-CH2- 또는 -C(=0)-이고, E2는 -C(R9)(R10)- 또는 -NR11-C(=0)인데, 위의 카르보닐기는 NR6에 결합되고, R9및 R10은 각각 수소 또는 C1-6알킬이거나, R9또는 R10은 함께, 1또는 2의 C1-6알킬로 치환될 수 있는 C4-6알칸디일을 형성할 수 있고, D1,D2및 E1기중의 1 또는 2의 수소원자는 C1-6알킬로 치환될 수 있고, R11은 수소 또는 C1-6알킬이고, R12는 수소, C1-6알킬 또는 C1-6알킬티오이고, R13은 수소 또는 C1-6알킬티오이고, 아릴은, 할로, C1-6알킬, C1-6알킬옥시, 히드록시 및, 모노, 디 또는 트리할로 C1-6알킬로 이루어진 그룹으로부터 선택한 1내지 3의 기로 치환될 수 있는 페닐이다.
  2. 제1항에 있어서, Y가 식(a), (b), (c), (d) 또는 (e)이고; R5및 R6의 각각 C1-6알킬, C3-7시클로알킬, (아릴)C1-6알킬로서 이들은 C1-6알킬 또는 C3-7시클로알킬부위가 옥소 또는 히드록시로 치환될 수 있거나, R5및 R6이 각각 C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로, C1-6알킬인, 5-리폭시게나제 억제성 약제조성물.
  3. 제2항에 있어서, Y가 식(a)의 기이고, R5가 C1-6알킬이고, A-B가 CH=CH, (CH2)3또는 C(CH3)2-CH2이거나; Y가 식(b)의 기이고, R6이 C1-6알킬이고, A-B가 CH2-CH2(여기서 1또는 2의 수소는 C1-6알킬로 치환되거나 한쌍의 수소는 C4-6알칸디일로 치환될 수 있음)이거나 Y가 식(c)의 기이고, X가 0이고, R6이 C1-6알킬, (아릴)C1-6알킬, C3-7시클로알킬, 모노, 디 또는 트리할로 C1-6알[상기 C1-6알킬, (아릴) C1-6알킬 및 C3-7시클로알킬은 C1-6알킬 또는 C3-7시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있음]이고, D1=D2가 CH=N(여기서 수소는 C1-6알킬로 치환될 수 있음)이거나; Y가 식(d)의 기이고, X가 0이고, R6이 C1-6알킬 또는 (아릴) C1-6알킬(상기 두기는 C1-6알킬 부위가 옥소 또는 히드록시로 치환될 수 있음)이거나 Y가 식(e)의 기이고, R6이 C1-6알킬 또는 (아릴) C1-6알킬(상기 두기는 C1-6알킬부위가 옥소 또는 히드록시로 치환될 수 있음)인, 5-리폭시게나제 억제성 약제조성물.
  4. 제3항에 있어서, 화합물이 2,4-디히드로-4-[4-[4-(4-히드록시-3,5-디메틸-페닐)-1피페라지닐]페닐]-5-메틸-2-(1-메틸프로필)-3H-1,2,4-트리아졸-3-온, 2,4-디히드로-4-[4-[4-(4-히드록시페닐)-1-피페라지닐]페닐]-5-메틸-2-(1-메틸프로필)-3H-1,2,4-트리아졸-3-온, 2-[2-(4-브로모페닐)-1-메틸-2-옥소에틸]-2,4-디히드로-4-[4-[4-(4-히드록시-3,5-디메틸페닐)-1-피페라지닐]페닐]-5-메틸-3H-1,2,4-트리아졸-3-온, 2-[2-(4-브로모페닐)-1-메틸-2-옥소에틸]-2,4-디히드로-4-[4-[4-(4-히드록시페닐)-1-피페라지닐]페닐]-5-메틸-3H-1,2,4-트리아졸-3-온, 2-[2-(4-브로모페닐)-1-메틸-2-옥소에틸]-2,4-디히드로-4-[4-[4-(4-히드록시페닐)-1-피페라지닐]페닐]-5메틸-3H-1,2,4-트리아졸-3-온, 2-[2-(4-브로모페닐)-2-히드록시-1-메틸에틸]-2,4-디히드로-4-[4-[4-(4-히드록시-페닐)-1-피페라지닐]페닐]-5-메틸-3H-1,2,4-트리아졸-3-온 또는 2-[2-(4-브로모페닐)-2-히드록시-1-메틸에틸]-2,4-디히드로-4-[4-[4-(4-히드록시-3,5-디메틸페닐)-1-피페라지닐]페닐]-5-메틸-3H-1,2,4-트리아졸-3-온인, 5-리폭시게나제 억제성 약제조성물.
  5. 유효성분으로 일반식(I)의 화합물. 그 산부가염 또는 그 입체이성체와 담체를 균일하게 혼합하여, 5-리폭시게나제 억제성 약제조성물을 제조하는 방법.
    위의 일반식에서, R1및 R2는 각각 수소, C1-6알킬 또는 할로이고, R3 및 R4는 각각 수소, 할로, 아미노, 니트로 또는 트리플루오르메틸이고, Y는 수소, 니트로, 아미노, 모노 또는 디(C1-6알킬)아미노, C1-6알킬 카르보닐아미노, C1-6알킬, C1-6알킬카르보닐, 히드록시, 할로, 모노 또는 디(C1-6알킬) 아미노설포닐 또는 다음식의 복소환기이고,
    X는 O 또는 S이고, R5및 R6은 각각 C1-6알킬, C3-6알케닐, C3-6알키닐, 아릴, (아릴)C1-6알킬, C3-7시클로알킬(C3-7시클로알킬) C1-6알킬, C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로 C1-6알킬인데, 위의 C1-6알킬, C3-7시클로알킬, (C3-7시클로알킬) C1-6알킬 및 (아릴) C1-6알킬은 C1-6알킬 또는 C3-7시클로알킬 부위의 탄소원자에서 옥소 또는 히드록시로 치환될 수 있으며, 단 상기 탄소원자는 R5또는 R6와 결합한 질소원자에 인접하여 있지 않고, R6은 수소일 수 있으며, A는 -C(R7)(R8)-이고, B는 -CH2-또는-CH2-CH2-이거나, A와 B는 함께 -CH=CH-(1) 또는 -CH=N-(m)의 2가지기를 형성하며, 이들 기의 탄소원자는 X와 결합하고, R7및 R8은 각각 수소 또는 C1-6알킬이거나, R7은 C1-6알킬옥시이고, -B-,-CH=CH-(1) 및-CH=N-(m)중의 1 또는 2의 수소원자는 C1-6알킬 또는 아릴로 치환될 수 있고, B기중에서 한쌍의 수소원자는, 1 또는 2의 C1-6알킬로 치환될 수 있는, C4-6알칸디일로 치환될 수 있고, D1은 -N= 또는 -CH-이고, D2는 -N=,=CH- 또는 =CH-C(=0)-이고, E1-CH2-,-CH2-CH2- 또는 -C(=0)-이고, E2는 -C(R9)(R10)- 또는 -NR11-C(=0)인데, 위의 카르보닐기는 NR6에 결합되고, R9및 R10은 각각 수소 또는 C1-6알킬이거나, R9및 R10은 함께, 1 또는 2의 C1-6알킬로 치환될 수 있는 C4-6알칸디일을 형성할 수 있고, D1,D2및 E1기중의 1 또는 2의 수소원자는 C1-6알킬로 치환될 수 있고, R11은 수소 또는 C1-6알킬이고, R12는 수소, C1-6알킬 또는 C1-6알킬티오이고, R13은 수소 또는 C1-6알킬티오이고, 아릴은, 할로, C1-6알킬, C1-6알킬옥시, 히드록시 및, 모노, 디 또는 트리할로 C1-6알킬로 이루어진 그룹으로부터 선택한 1 내지 3의 기로 치환될 수 있는 페닐이다.
  6. 일반식(I-a)의 화합물, 그 산부가염 또는 그 입체화학이성체.
    위의 일반식에서, R1및 R2는 각각 수소, C1-6알킬 또는 할로인데, 단, R1및 R2중 1이상은 C1-6알킬 또는 할로이고, R3및 R4는 각각 수소, 할로, 아미노, 니트로 또는 트리플루오로메틸이고, R5및 R6는 각각 C1-6알킬, C3-6알케닐, C3-6알키닐, 아릴, (아릴)C1-6알킬, C3-7시클로알킬, (C3-7시클로알킬)C1-6알킬, C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로 C1-6알킬인데, 위의 C1-6알킬, C3-7시클로알킬, (C3-7시클로알킬)C1-6알킬 및 (아릴)C1-6알킬은, C1-5알킬 또는 C3-7시클로알킬 부위의 탄소원자에서 옥소 또는 히드록시로 치환될 수 있으며, 단 상기 탄소원자는 R5또는 R6과 결합한 질소원자에 인접하여 있지 않고, R6은 수소일 수 있으며, R7및 R8은 각각 수소 또는 C1-6알킬이거나, R7은 C1-6알킬옥시이고, R9은 R10은 각각 수소 또는 C1-6알킬이거나, R9및 R10은 함께 1 또는 2의 C1-6알킬로 치환될 수 있는 C4-6알 켄디일을 형성할 수 있고, R11은 수소 또는 C1-6알킬이고, R12는 수소, C1-6알킬 또는 C1-6알킬티오이고, R13은 수소 또는 C1-6알킬티오이고, Y는 모노 또는 디(C1-6알킬 )아미노, (C1-6알킬)카르보닐아미노, C1-6알킬, C1-6알킬카르보닐, 할로, 모노 또는 디(C1-6알킬) 아미노설포닐 또는 다음식의 복소환기이고,
    위의 식에서 R5, R6및 R11은 이미 정의한 바와 같고, X는 O또는 S이고, A는 -C(R7)(R8)-이고, B는 -CH2- 또는 -CH2-CH2-이거나, A와 B는 함께 -CH=CH-(1) 또는 -CH=N-(m)의 2가기를 형성하며, 이들기의 탄소원자는 X와 결합하고, D2는 -N=,=CH- 또는 =CH-C(=0)-이고, E1은 -CH2-,CH2,CH2- 또는 -C(=0)-이고, E2는 -C(R9)(R10)- 또는 -NR11-C(=0)인데, 위의 카르보닐기는 NR6에 결합되고,D2및 E1기중의 1또는 2의 수소원자는 C1-6알킬로 치환될 수 있고, R5-a는 모노, 디 또는 트리할로 C1-6알킬; C7시클로알킬 또는 (C7시클로알킬)C1-6알킬이고, 위의 두기는 C1-6알킬 또는 C7시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, R5-b는 C1-6알킬, C3-7시클로알킬, 또는 (C3-7시클로알킬)C1-6알킬 또는 (아릴)C1-6알킬이고, 이들은 모두 C1-6알킬 는 C3-6시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, B1은 -CH2-CH2이고, 여기서 1 또는 2의 수소는 C1-6알킬 또는 아릴로 치환되거나, 한쌍의 수소는 1 또는 2의 C4-6알칸디일로 치환될 수 있고, D1-a는 =CH- 또는 =CH-C(=0)이고, 여기서 수소 원자는 C1-6알킬이고, R14는 수소 또는 C1-6알킬이고, R6-a는 C3-6알케닐, C3-6알키닐, 아릴 C3-7시클로알킬, (C3-7시클로알킬)C1-6알킬, C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로 C1-6알킬; C7시클로알킬 또는 (C7시클로알킬)C1-6알킬이고, 상기 두기는 C1-6알킬 또는 C7시클로알킬부위가 옥소 또는 히드록시로 치환될 수 있고, R6-b는 C1-6알킬, (아릴)C1-6알킬이거나 C1-6알킬, C3-6시클로알킬, (C3-6시클리로알킬) C1-6알킬 또는 (아릴)C1-6알킬이고, 이들은 C1-6알킬 또는 C3-6시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, R6-c는 모노, 디 또는 트리할로 C1-6알킬; C7시클로알킬 또는 (C7시클로알킬)C1-6알킬이고, 이들은 C1-6알킬 또는 C7시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있거나, R6-c및 R9는 1 또는 2의 알킬로 치환될 수 있는 C3-5알칸디일을 형성할 수 있고, E1-a는 -CH2-CH2-이고, 여기서 1 또는 2의 수소는 C1-6알킬로 치환될 수 있고, R6-d는 수소, C3-6알케닐, C3-6알키닐, 아릴, C3-6시클로알킬, (C3-6시클로알킬)C1-6알킬, C1-6알킬옥시 C1-6알킬이거나, C1-6알킬, C3-6시클로알킬, (C3-6시클로알킬)C1-6알킬 또는 (아릴)C1-6알킬이고, 이들 모두는 C1-6알킬 또는 C3-6시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, E2-a는 -NR11-C(=0)이고, 아릴은, 할로, C1-6알킬, C1-6알킬옥시, 히드록시 및 모노, 디 또는 트리할로 C1-6알킬로 이루어진 그룹으로부터 선택한 1 내지 3의 기로 치환될 수 있는 페닐이다.
  7. 제6항에 있어서, R1,R2중의 하나 이상의 C1-4알킬 또는 할로이고, R3,R4중의 하나 이상이 할로, 아미노, 니트로 또는 트리플루오로메틸이고, Y가 다음식의 기이고,
    위의 식에서 A,B,D2,R10및, R11은 정의한 바와 같고, R15는 C1-6알킬이고, R16은 모노, 디 또는 트히할로 C1-6알킬; C3-6 시클로알킬; 또는 옥소로 치환될 수 있는 C7시클로알킬이고, E3은 C3-5알칸디일이고, E4는 C4-6알칸디일이고, R1 7은 (아릴)C1-6알킬인데, C1-6알킬부위가 옥소 또는 히드록시로 치환될 수 있는 일반식(I-a)의 화합물, 그 산부가염 또는 그 입체화학이성체.
  8. 제7항에 있어서, R1,R2중의 하나 이상의 메틸이고, Y가 식 (c-1a),(e-1a) 또는 (e-wa)인, 일반식(I-a)의 화합물, 그 산부가염 또는 그 입체화학 이성체.
  9. a) 일반식(II)의 알콕시유도체를 산성매질중에서 강한 친핵성 화합물로 탈알킬화하거나 b) 일반식(III)의 피페라진을 일반식(Ⅳ)의 치환된 벤젠으로 N-알킬화하여, 일반식(I-a)의 화합물, 그 산부가염 또는 그 입체화학 이성체를 제조하는 방법.
    위의 식에서, R1및 R2는 각각 수소, C1-6알킬, 또는 할로인데, 단 R1및 R2중의 1이상은 C1-6알킬 또는 할로이고, R3및 R4는 각각 수소, 할로, 아미노, 니트로 또는 트리플루오로메틸이고, Y는 모노 또는 디(C1-6알킬) 아미노, (C1-6알킬) 카르보닐아미노, C1-6알킬, C1-6알킬카르보닐, 할로, 모노 또는 디(C1-6알킬) 아미노설포닐 또는 다음식의 복소환기이고,
    위의 식에서 R5,R6및 R11은 이미 정의한 바와같고, X는 O또는 S이고, A는 -C(R7)(R8)-이고, B는 -CH2-또는 -CH2-CH2-이거나, A와 B는 함께 -CH=CH-(1) 또는 -CH=N=(m)의 2가기를 형성하며, 이들 거의 탄소원자는 X와 결합하고, D2는 -N=, =CH- 또는 =CH- 또는 =CH-C(=0)-이고, E1은 -CH2-,-CH2-CH2- 또는 -C(=0)-이고, E2는 -C(R9)(R10)- 또는 -NR11-C(=0)인데, 위의 카르보닐기는 NR6에 결합되고, D2및 E1기중의 1 또는 2의 수소원자는 C1-6알킬로 치환될 수 있고, R5-a는 모노, 디 또는 트리할로 C1-6알킬; C7시클로알킬 또는 (C7시클로알킬)C1-6알킬이고, 위의 두기는 C1-6알킬 또는 C7시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, R5-b는 C1-6알킬, C3-6시클로알킬, 또는 (C3-6시클로알킬)C1-6알킬 또는 (아릴)C1-6알킬이고, 이들은 모두 C1-6알킬 또는 C3-6시클로알킬 부위가 옥소 또는 히드록시로 치환될 수 있고, R18은 C1-6알킬이고, W는 반응이탈기이다.
  10. 일반식(I)의 화합물, 그 산부가염 또는 그 입체화학 이성체를 5-리폭시나게나제 억제 효과량으로 류코트리엔(leukotriene)관련 질환 또는 장애중의 온혈동물에 투여하여 치료하는 방법.
    위의 일반식에서, R1및 R2는 각각 수소, C1-6알킬 또는 할로이고, R3및 R4는 각각 수소, 할로, 아미노, 니트로 또는 트리플루오로메틸이고, Y는 수소, 니트로, 아미노, 모노 또는 디(C1-6알킬) 아미노, C1-6알킬 카르보닐아미노, C1-6알킬, C1-6알킬카르보닐, 히드록시, 할로, 모노 또는 디(C1-6알킬) 아미노설포닐 또는 다음식의 복소환기이고,
    x는 O 또는 S이고, R5및 R6은 각각 C1-6알킬, C3-6알케닐, C3-6알키닐, 아릴, (아릴)C1-6알킬, C3-7시클로알킬(C3-7시클로알킬) C1-6알킬, C1-6알킬옥시 C1-6알킬, 모노, 디 또는 트리할로 C1-6알킬인데, 위의 C1-6알킬, C3-7시클로알킬, (C3-7시클로알킬) C1-6알킬 및 (아릴) C1-6알킬은 C1-6알킬 또는 C3-7시클로알킬 부위의 탄소원자에서 옥소 또는 히드록시로 치환될 수 있으며, 단 상기 탄소원자는 R5또는 R6과 결합한 질소원자에 인접하여 있지 않고, R6은 수소일 수 있으며, A는 -C(R7)(R8)-이고, B는 -CH2- 또는 -CH2-CH2-이거나 A와 B는 함께 -CH-CH-(1) 또는 -CH=N-(m)의 2가기를 형성하며, 이들 기의 탄소원자는 X와 결합하고, R7및 R8은 각각 수소 또는 C1-6알킬이거나, R7은 C1-6알킬옥시이고, -B-, -CH=CH-(1) 및 -CH=N(m)중의 1 또는 2의 수소원자는 C1-6알킬 또는 알킬로 치환될 수 있고, B기중에서 한쌍의 수소원자는, 1 또는 2의 C1-6알킬로 치환될 수 있는, C4-6알칸디일로 치환될 수 있고, D1은 -N= 또는 -CH-이고, D2는 -N=,=CH- 또는 =CH- 또는 =CH-C(=0)-이고, E1은 -CH2-,-CH2-CH2- 또는 -C(=0)-이고, E2는 -C(R9)(R10)- 또는 -NR11-C(=0)인데, 위의 카르보닐기는 NR6에 결합되고, R9및 R10은 각각 수소 또는 C1-6알킬이거나, R9및 R10은 함께, 1또는 2의 C1-6알킬로 치환될 수 있는 C4-6알칸디일을 형성할 수 있고, D1,D2는 수소, C1-6알킬로 치환될 수 있고, R11은 수소 또는 C1-6알킬이고, R12는 수소, C1-6알킬 또는 C1-6알킬티오이고, R13은 수소 또는 C1-6알킬티오이고, R13은 수소 또는 C1-6알킬티오이고, 아릴은, 할로, C1-6알킬, C1-6알킬옥시, 히드록시 및, 모노, 디 또는 트리할로 C1-6알킬로 이루어진 그룹으로부터 선택한 1 내지 3의 기로 치환될 수 있는 페닐이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019890002435A 1988-02-29 1989-02-28 5-리폭시게나제 억제성 4-(4-페닐-1-피페라지닐)페닐유도체 KR0133074B1 (ko)

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IE63150B1 (en) 1995-03-22
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DK91889A (da) 1989-08-30
ZA891547B (en) 1990-10-31
PH26574A (en) 1992-08-19
PT89875A (pt) 1989-10-04
JPH023678A (ja) 1990-01-09
ES2056190T3 (es) 1994-10-01
HU9303071D0 (en) 1994-01-28
EP0331232B1 (en) 1994-05-18
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MY103802A (en) 1993-09-30
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NO174049B (no) 1993-11-29
IL89426A (en) 1993-06-10
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US4931444A (en) 1990-06-05
IL89426A0 (en) 1989-09-10
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AU3073989A (en) 1989-08-31
PT89875B (pt) 1994-04-29
FI890931A (fi) 1989-08-30
FI890931A0 (fi) 1989-02-27
BG49940A3 (en) 1992-03-16
DE68915308T2 (de) 1994-10-06

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