KR950702551A - 염증 및 면역 질환의 치료용 2,5-디아릴 테트라히드로티오펜, 2,5-디아릴 테트라히드로푸란 및 그 유사물(2,5-diaryl tetrahydro-thiophene, furans and analogs for the treatment of inflamimatory and immune disorders) - Google Patents

염증 및 면역 질환의 치료용 2,5-디아릴 테트라히드로티오펜, 2,5-디아릴 테트라히드로푸란 및 그 유사물(2,5-diaryl tetrahydro-thiophene, furans and analogs for the treatment of inflamimatory and immune disorders)

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KR950702551A
KR950702551A KR1019950700145A KR19950700145A KR950702551A KR 950702551 A KR950702551 A KR 950702551A KR 1019950700145 A KR1019950700145 A KR 1019950700145A KR 19950700145 A KR19950700145 A KR 19950700145A KR 950702551 A KR950702551 A KR 950702551A
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alkyl
lower alkyl
alkenyl
halo
alkynyl
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KR1019950700145A
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지옹 싸이
산-바오 황
데이비드 킬리안
티. 와이 쉔
후소인 사이자트
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스티븐 입
싸이토메드 인코오포레이티드
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Priority claimed from US07/912,788 external-priority patent/US5358938A/en
Priority claimed from US07/933,991 external-priority patent/US5434151A/en
Application filed by 스티븐 입, 싸이토메드 인코오포레이티드 filed Critical 스티븐 입
Priority claimed from PCT/US1993/006575 external-priority patent/WO1994001430A1/en
Publication of KR950702551A publication Critical patent/KR950702551A/ko

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Abstract

본 발명은 염증 또는 면역 반응성 다형핵 백혈구의 손상성 산소 라디칼을 형성시키는 주화성 및 호흡 폭발을 감소시키는 2,5-디아릴 테트라히드로푸란, 2,5-디아릴 테트라히드로티오펜, 2,4-디아릴 테트라히드로푸란, 2,4-디아릴 테트라히드로티오펜, 1,3-디아릴 시클로펜탄, 2,4-디아릴 피롤리딘 및 2,5-디아릴 피롤리딘을 개시한다. 상기 화합물은 PAF 수용기 길항 물질로써 작용하므로쏘, 효소 5-리폭시게나제를 억제시키므로써, 또는 이중 활성을 나타내므로써, 즉 PAF 수용기 길항 물질로서 그리고 5-리폭시게나제의 억제제로서 작용하므로써, 상기 생물학적 활성을 나타낸다. 본 발명은 또한 PAF 또는 류코트리엔에 의해 매개되는 질환의 치료 방법을 개시하는데, 이 방법은 약학적 허용 담체내에 함유될 수도 있는 1종 이상의 상기 화합물 또는 그들의 약학적 허용염의 유효량을 투여하는 것을 포함한다.

Description

염증 및 면역 질환의 치료용 2,5-디아릴 테트라히드로티오펜, 2,5-디아릴 테트라히드로푸란 및 그 유사물(2,5-DIARYL TETRAHYDRO-THIOPHENE, FURANS AND ANALOGS FOR THE TREATMENT OF INFLAMIMATORY AND IMMUNE DISORDERS)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 3,4,5-트리메톡시페닐비닐케톤(화합물 106, 제1도)의 제조방법을 도식적으로 예시한 것이다,
제2도는 트란스-2-(3,4-디메톡시-5-아미노에틸티오페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 1, 제2도) 및 트란스-2-(3,4-디메톡시-5-아미노에틸 설포닐페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 2, 제2도)의 제조방법을 도식적으로 예시한 것,
제3도는 트란스-2-(3-메톡시-4-프로폭시-5-아미노페닐)-5-아미노페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로푸란(화합물 122, 제3도), 트란스-2-(3,4-디메톡시-5-아미노페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 123, 제3도) 및 트란스-2-(3-메톡시-4-프로폭시-5-아미노페닐)-5-(3,4,5-트리메톡시페닐)테트라히드로티오펜(화합물 124, 제3도)의 제조방법을 도식적으로 예시한 것이다,
제4도는 트란스-2-(3-메톡시-4-프로폭시-5-벤질아미노페닐)-5-(3,4,5-트리메톡시페닐)테트라히드로푸란(화합물 3, 제4도), 트란스-2-(3-메톡시-4-프로폭시-5-히드록시에틸아미노페닐)-5(3,4,5-트리메톡시페닐)-테트라히드로푸란(화합물 4, 제4도), 트란스-2-(3-메톡시-4-프로폭시-5-N,N-디알릴아미노페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로푸란(화합물 5, 제4도), 트란스-2-(3,4-디메톡시-5-벤질아미노페닐)-5-(3,4,5-트리메톡시페닐)테트라히드로 티오펜(화합물 6, 제4도), 트란스-2-(3-메톡시-4-프로폭시-5-히드록시에틸아미노페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 7, 제4도), 트란스-2-(3,4-디메톡시-5-히드록시에틸아미노페닐)-5-(3,4,5-트리메톡시페닐)테트라히드로티오펜(화합물 8, 제4도), 트란스-2-(3-메톡시-4-프로폭시-5-히드록시에틸 아미노페닐)-5-(3,4,5-트리메톡시 페닐)-테트라히드로티오펜(화합물 9, 제4도), 트란스-2-1,3,4-디메톡시-5-N-디알릴아미노페닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 10, 제4도), 및 트란스-2-(3-메톡시-4-프로폭시-5-N,N-디알릴아미노페닐-5-(3,4,5-트리메톡시페닐)테트라히드로티오펜(화합물 11, 제4도), 및 시스- 및 트란스-2-[N'-히드록실-N'-(치환된)]-'2-프로폭시-3-메톡시-5-(5-(3,4,5-트리메톡시페닐)-(테트라히드로푸란 또는 테트라히드로 티오펜)]-페닐]-우레아(화합물 12-32 및 38-41, 제4도)의 제조 방법을 도식적으로 예시한 것이다,
제5도는 트란스-2-(3-메톡시-4-프로폭시-5-히드록시에틸설포닐)-5-(3,4,5-트리메톡시페닐)-테트라히드로티오펜(화합물 38)의 제조 방법을 도식적으로 예시한 것이다.

Claims (48)

  1. 하기 일반식(I)의 화합물 :
  3. X는 O, S, S(O), S(O)2, CR9또는 NR10인데; 여기서, W는 독립적으로 (1) -AN(OM)C(O)N(R3)R4, -AN(R3)C(O)N(OM)R4, -AN(OM)C(O)R4, -AC(O)N()OM)R4, -N(OM)C(O)N(R3)R4, -N(R3)C(O)N(OM)R4, -N(OM)C(O)R4, -C(O)N(OM)R4,-OR6N(R5)R6-(C5H4N)R6R7, -OR6N(COR5)R6-(C5H4N)R6R7, -OR6OC(O)N(COR5)R6-(C5H4N)R6R7, -OR6OC(O)N(COR5)R6(C5H4N)R6R7, -OR6O(CO)N(CO2R6)R6(C5H4N)R6R7, -A(C5H4N)R6R7,, 또는 -OR6N(CO2R5)R6-(C5H4N)R6R7; (2) 하기 일반식의 아미도히드록시우레아; -(R19)C(O)C(R19)2N(OM)C(O)NHR20, -C(O)N(R19)C(R19)2N(OM)C(O)NHR20, -AN(R19)C(O)C(R10)2N(OM)C(O)NHR20, -AC(O)N(R19)2N(OM)C(O)NHR20, -NHC(O)N(OM)C(R19)2또는 -NHC(O)N(OM)C(R19Y)2C(O)N(R19)2또는 -NHC(O)N(OM)C(R19)2N(R19)C(O)R19; (3) 하기 구조를 갖는 옥스알칸:
  5. (여기서 n 및 m은 독립적으로 1 내지 4임); (4) 하기 구조를 갖는 티오알칸:
  7. 또는 (5) 하기 구조를 갖는 퀴놀릴메톡시이고;
  9. n은 1 도는 2이고; m은 1,2 또는 3이고; p는 0 또는 1이며; 이때, A는 알킬, 알케닐, 알키닐, 알크아릴, 아르알킬, 할로 저급 알킬, 할로 저급 알케닐, 할로 저급 알키닐, -C1-10(옥시)C1-10알킬, -C1-10알킬(티오)C1-10알킬, -N(R3)C(O)알킬, -N(R3)C(O)알케닐, -N(R3)C(O)알키닐, -N(R3)C(O)(알킬)옥시(알킬), -N(R3)C(O)(알킬)티오(알킬), -N(R3)C(O)N(알킬), N-(R3)C)O)N(알케닐), -N(R3)C(O)N(알키닐), -N(R3)C(O)N(알킬)옥시(알킬), -N(R3)C(O)N(알킬)티오(알킬), N(R3)C(O2)알킬, -N(R3)C(O2)알케닐, -N-(R3)C(O2)알키닐, -N(R3)C(O2)(알킬)옥시(알킬), -N(R3)C(O2)(알킬)티오(알킬), -OC(O2)알킬, -OC(O2)알케닐, -OC(O2)알키닐, -OC(O2)(알킬)옥시(알킬), -OC(O2)(알킬)티오(알킬), -N(R3)C(S)알케닐, -N(R3)C(S)알키닐, -N(R3)C(S)(알킬)옥시(알킬), -N(R3)C(S)(알킬)티오(알킬), -N(R3)C(S)N(알킬), -N(R3)C(S)N(알케닐), -N(R3)C(S)N(알키닐), -N(R3)C(S)N(알킬)옥시(알킬), -N(R3)C(S)N(알킬)티오(알킬), -N(R3)C(S)S(알킬), -N(R3)C(S)S(알케닐), -N(R3)C(S)S(알키닐), N(R3)C(S)S(알킬)옥시(알킬), -N(R3)C(S)S(알킬)티오(알킬), -SC(S)S(알킬), -SC(S)S(알키닐), -SC(S)S(알케닐), -SC(S)S(알킬)옥시(알킬) 및 -SC(S)S(알킬)티오(알킬)이고; M은 수소, 약학적 허용 양이온 또는 대사에 의해 절단될 수 있는 이탈기이며; 상기 Ar1및 Ar2의 식에서, Y는 독립적으로 (a) 수소; (b) R1-6, R8, R10, -OR3, -OR11, -OR12, R3S-, R5S-, R5SO-, R3SO2-, R5SO2-, CF3O-, CF3S-, CF3SO-, -CF3SO2, -OCH2옥시시클로프로필, -OCH2C(O)OR3, OCH2OR3, -OCH2C(O)R3, -OCH2C3-8시클로알킬, -OCH2CH(R)R3, -OCH2시클로프로필, OCH2-아릴, -COH2CH(OH)CH2OH, 아릴-CH2-SO2-, (R3)2CHCH2SO2-, -CH2CH(OH)CH2OH, CF3SO2-, R3R4N-, -OCH2CO2R3, -NR3COR3, -OCONH2, -COONR3R4, -CONH2, -CONR3R4, -CR3R3R4, -SO2NR3R4, -SONR3R4, -CH3OCH2NR3R6, -SNR3R4, -CO2R3, -NR3R4SO2R3, -NR3R4SOR, -CO R3, -CONR3, -NO2, -CN, -N(R5)CONR3R4, -CH2N(R5)CONR3R4, -R6NR3R4, -OR6NR3N4, -O(O)CR5, -O(O)CNR3R4, -OR6NO, -SR6NR3R4, -S(O)R6NR3R4, -SO2R6NR3R4, -SO2OR6CON, -S(O)R6OH, -OR6OC(O)N(CO2R6)R6; O-알킬-N-(아릴)-C(O)-헤테로사이클; O-알킬-O-아릴O-알킬-S-아릴; S-알킬-O-아릴; 또는 S-알킬-S-아릴; (c) 상기 (b)에서 기술한 기로 치환될 수도 있는 헤테로사이클, 예를들면, 피릴, 푸릴, 피리딜, 1,2,4-티아디아졸릴, 피리미딜, 티에닐, 이소티아졸릴, 이미다졸릴, 테트라졸릴, 피라지닐, 피리미딜, 퀴놀릴, 이소퀴놀릴, 벤조티에틸, 이소벤조푸릴, 피라졸릴, 인돌릴, 퓨리닐, 카르바졸릴, 벤즈이미다졸릴, 및 이속사졸릴;
  11. (여기서, x1은 F, Cl, Br 및 I와 같은 할로; -C(O)아릴; CF3; OR3; -NR3C(O)R3; -OC(O)NH2: -CR3R3R4; -C(O)R3; -CH2OR3: -CH2CO2R3; -CH2OC(O)R3; R3CH(R3)CH2SO3; -NHCH2COOR3; N+R3R3R4R7; -NR3SO2R3; C(O)R3: NO2; 또는 CN; 또는
  13. 이때, R13, R14및 R15는 독립적으로 B가 -CH2-옥사시클로프로필, -CH2OR3, -CH2C(O)R3, -CH2CH(R3)R3, -CH2아릴, -CH2CH(OH)CH2OH; R3C(R3)2CH2SO2인 BO-를 의미하거나; R13-R14또는 R14-R15는 함께 연결되어 OCHR2CHR2-S(O)n(여기서, n은 0 내지 3임)와 같은 다리를 형성함);
  15. (여기서, x'은 할로, -C(O)아릴, -CF3또는 -OR3; -CH2OR3; -CH2CO2R3; -CH2CO(O)R3; -NHCH2COOR3; 또는 -N+R3R3R4R7임)이며; 상기 일반식에서, R1및 R2는 독립적으로 수소, 할로겐, 저급 알킬, 할로 저급 알킬, 할로, -COOH; -CONR16R17(여기서, R16및 R17은 독립적으로 C1-6알킬 및 수소를 의미함); -COOR3; 알케닐; C(O)R3; -CH2OR3; 저급 알키닐; -CH2NR4R3; =O; -OR3; 또는 -NR3R3이고; R3및 R4는 독립적으로 고리 및 비고리형 알킬, 알케닐, 알키닐, 아릴, 아르알킬, 알크아릴, 수소, C1-6알콕시-C1-10알킬, C1-6알킬티오-C1-10알킬, 및 C1-10치환된 알킬(여기서, 치환체는 독립적으로 히드록시 또는 카르보닐로서 C1-10중 임의의 탄소에 위치함)이고; R5는 고리 및 비고리형 저급 알킬, 저급 알케닐, 저급 알키닐, 할로 저급 알킬, 할로 저급 알케닐, 할로 저급 알키닐, 아르알킬 또는 아릴이고; R6는 고리 및 비고리형 저급 알킬, 저급 알케닐, 저급 알키닐, 아르알킬, 할로 저급 알킬, 할로 저급 알케닐, 할로 저급 알키날 또는 아릴이고; R7은 유기 또는 무기 음이온이고; R8은 할로 알킬, 할로저급 알킬, 할로 저급 알케닐, 할로 저급 알키닐, 저급 알케닐, 저급 알키닐, 아르알킬 또는아릴이고; R9는 독립적으로 수소, 할로겐, 저급 알킬, 할로 저급 알킬, 저급 알케닐, 저급 알키닐, -CONR3R4, -C(O)R5, -CO2R5, -CH2OR5, -CH2NR5R5, -CH2SR5, =O, =NR5, -NR3R4, -NR3R4R7또는 -OR5이고; R10는 -R3, -R8, -C(O)N(OR3)R3또는 -OR3이고; R11은 C1내지 C12알킬; 치환체가 히드록시 및 아미노로 구성된 군에서 선택되는 치환된 C1내지 C12알킬, 알케닐, 저급 알콕시-알킬; 알킬카르보닐 알킬, ③알킬아미노, -알킬아미노(알킬 또는 디아킬), 저급 알킬 S(O)m 저급 알킬(여기서, m은 0,1 또는 2임); 이미다졸릴 저급 알킬, 모폴리닐 저급알킬, 티아졸리닐 저급 알킬, 피페리디닐 저급 알킬, 이미다졸릴카르보닐, 모폴리닐 카르보닐, 모폴리닐(저급 알킬)아미노 카르보닐, N-피릴피리디닐-저급알킬; 피리딜티오-저급 알킬; 모폴리닐-저급 알킬; 히드록시페닐티오-저급알킬; 아미다졸릴티오-저급알킬; 트리아졸리티오-저급아킬; 트리아졸릴페닐 티오-저급 알킬; 테트라졸리티오-저급알킬; 테트라졸릴페닐티오-저급알킬; 아미디노페닐티오-조급 알킬; 페닐-S(O)g-저급 알킬-; (R3O)d-페닐-S(O)g-저급알킬-; (R3R3N)D페닐-S(O)g-저급 알킬-; (CN)d-페닐-S(O)g-저급 알킬-; (CN)d-페닐-S(O)g-저급 알킬-; (할로)d-페닐-S(O)g-저급 알킬-; (R3COO)d-페닐-S(O)g-저급 알킬-; (R3COO)d-페닐-S(O)g-저급 알킬-; (R3CO)d-페닐-S(O)g-저급 알킬-; 페닐-O-저급 알킬-; (R3O)d-페닐-O-저급 알킬; (CN)d-페닐-O-저급 알킬-; (할로)d-페닐-O-저급 알킬-; (R3COO)d-페닐-O-저급 알킬-; (R3OCO)d-페닐-O-저급 알킬-; 또는 (R3CO)d-페닐-O-저급 알킬-(여기서 d는 1,12,3,4 또는 5이며, g는 0,1 또는 2임)이고; R12는 알킬; 치환체가 히드록시 및 아미노로 구성된 군에서 선택되는 치환된 알킬; -저급 알킬-O-R18(여기서, R18은 M+가 약학적 허용 양이온인 -PO2(OH)-M+ 또는 -PO3(M+)2임; -C(O)(CH2)2CO2-M+ 또는 -SO3-M+; -저급 알킬카르보닐-저급 알킬; -카르복시 저급 알킬; -저급 알킬아미노-저급 알킬; N,N-디치환딘 아미노-저급 알킬-(여기서, 치환체는 각각 독립적으로 저급 알킬을 의미함); 피리딜-저급 알킬; 이미다졸릴-저급 알킬; 이미다졸릴-Y-저급 알킬(여기서, Y는 티오 또는 아미노임); 모폴리닐-저급 알킬; 피롤리디닐-저급 알킬; 티아졸리닐-저급 알킬; 피페리디닐-저급 알킬; 모폴리닐-저급 히드록시알킬; N-피릴; 피페라지닐-저급 알킬; 치환체가 저급 알킬인 N-치환된 피페라지닐-저급 알킬; 트리아졸릴 저급 알킬; 테트라졸릴-저급 알킬; 테트라졸릴아미노-저급 알킬; 또는 티아졸릴-저급 알킬이고; R19는 H, 저급 알킬 또는 저급 알케닐이며; R20은 H, 할로겐, 저급 알콕시 또는 저급 알킬이다.
  16. 하기 일반식(II)의 화합물
  18. 상기 일반식에서, Ar3및 Ar4는 독립적으로
  20. X는 O, S, S(O), S(O)2, 또는 NR10이며; 상기 Ar3및 Ar4의 식에서, m은 1, 2 또는 3이고; t는 1,2, 3 도는 4이고; Z는 독립적으로 W 또는 Y이고; 모든 R기는 제1항에서 정의한 바와 같다.
  21. 하기 일반식(III)의 화합물
  23. 상기 일반식에서,
  25. 상기 Ar5의 식에서, v는 0,1 또는 2이고; Q는 치환체가 히드록시 및 아미노로 구성된 군에서 선택되는 치환된 C1내지 C12알킬, 알킬카르보닐알킬, 알킬; 저급 알킬 S(O)m-저급 알킬(여기서, m은 1 또는 2임); 이미다졸릴 저급 알킬, 모폴리닐 저급 알킬, 티아졸리닐 저급 알킬, 피페리디닐 저급 알킬, 이미다졸릴카르보닐, 모폴리닐 카르보닐, 아모폴리닐(저급 알킬)아미노카르보닐, N-피릴피리디닐-저급 알킬; 피리딜티오-저급 알킬; 모폴리닐-저급알킬; 히드록시페닐티오-저급 알킬; 시아노페닐티오-저급 알킬; 이미다졸릴티오-저급 알킬; 트리아졸릴티오-저급 알킬; 트리아졸릴 페닐티오-저급 알킬; 테트라졸릴티오-저급 알킬; 테트라졸리페닐티오-저급 알킬; 아미노페닐티오-저급 알킬; N,N-디치환된 아미노페닐티오 저급 알킬-(여기서, 아민 치환체는 각각 독립적으로 저급 알킬을 의미함); 아미노디노페닐티오-저급 알킬; 페닐설피닐-저급 알킬; 또는 페닐설포닐 저급 알킬; -저급 알킬-O-R18(여기서, R19은 M+가 약학적 허영 양이온인 -PO2(OH)-M+ 또는 -PO2(M+)2임; -C(O)(CH2)2CO2M+ 또는 -SO3M+; -저급 알킬카르보닐-저급 알킬; -카르복시 저급 알킬; -저급 알킬아미노-저급 알킬; 아민 치환체가 각각 독립적으로 저급 알킬을 의미하는 N,N-디치환된 아미노 저급 알킬; 피리딜-저급 알킬; 이미다졸릴-저급 알킬; 이미다졸릴-Y-저급 알킬(여기서, Y는 티오 또는 아미노임); 모폴리닐-저급 알킬; 피롤리디닐-저급 알킬; 티아졸리닐-저급 알킬; 피페리디닐-저급 알킬; 모폴리닐-저급 히드록시알킬; N-피릴; 피페라지닐-저급 알킬; 아민 치환체가 저급 알킬인 N-치환된 피페라지닐-저급 알킬; 트리아졸릴 저급 알킬, 테트라졸릴-저급 알킬; 테트라졸릴아미노-저급 알킬; 또는 티아졸릴-저급 알킬이다.
  26. 약학적 허용 담체내에 제1항의 화합물의 유효량을 함유하는 약학 조성물.
  27. 제2항에 있어서, 약학적 허용 담체를 추가로 함유하는 화합물.
  28. 제3항에 있어서, 약학적 허용 담체를 추가로 함유하는 화합물.
  29. 산소 라디칼의 형성을 감소시키기 위하여 약학적 허용 담체내의 제1항의 화합물의 유효량을 투여하는 것을 포함하는 혈소판 활성화 인자에 의해 또는 5-리폭시게나제의 생성물에 의해 매개되는 동물 질환의 치료 방법.
  30. 제7항에 있어서, 동물이 포유 동물인 방법.
  31. 제8항에 있어서, 포유 동물이 인간인 방법.
  32. 제8항에 있어서, 포유 동물이 말인 방법.
  33. 제8항에 있어서, 포유 동물이 개인 방법.
  34. 제8항에 있어서, 포유 동물이 소인 방법.
  35. 약학적 허용 담체내의 제2항의 화합물의 유효량을 투여하는 것을 포함하는 혈소판 활성화 인자에 의해 또는 5-리폭시게나제에 의해 매개되는 동물 질환의 치료 방법.
  36. 제13항에 있어서, 동물이 포유 동물인 방법.
  37. 제14항에 있어서, 포유 동물이 인간인 방법.
  38. 제14항에 있어서, 포유 동물이 말인 방법.
  39. 제14항에 있어서, 포유 동물이 개인 방법.
  40. 제14항에 있어서, 포유 동물이 소인 방법.
  41. 약학적 허용 담체내의 제2항의 화합물의 유효량을 투여하는 것을 포함하는, 혈소판 활성화 인자에 의해 또는 5-리폭시게나제의 생성물에 의해 매개되는 동물 질환의 치료 방법.
  42. 제19항에 있어서, 동물이 포유 동물인 방법.
  43. 제20항에 있어서, 포유 동물이 인간인 방법.
  44. 제20항에 있어서, 포유 동물이 말인 방법.
  45. 제20항에 있엇거, 포유 동물이 개인 방법.
  46. 제20항에 있어서, 포유 동물이 소인 방법.
  47. 트란스-2-[5-n'-메틸-n'-히드록시우레이딜메틸)-3-메톡시-4-P-클로로페닐티오-에톡시페닐]-5-(3,4,5-트리메톡시페닐)테트라히드로푸란.
  48. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950700145A 1992-07-13 1993-07-13 염증 및 면역 질환의 치료용 2,5-디아릴 테트라히드로티오펜, 2,5-디아릴 테트라히드로푸란 및 그 유사물(2,5-diaryl tetrahydro-thiophene, furans and analogs for the treatment of inflamimatory and immune disorders) KR950702551A (ko)

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Application Number Priority Date Filing Date Title
US07/912,788 US5358938A (en) 1992-07-13 1992-07-13 Compounds and methods for the treatment of disorders mediated by platelet activating factor or products of 5-lipoxygenase
US07/912788 1992-07-13
US07/933991 1992-08-24
US07/933,991 US5434151A (en) 1992-08-24 1992-08-24 Compounds and methods for the treatment of disorders mediated by platelet activating factor or products of 5-lipoxygenase
US08/062,391 US5648486A (en) 1992-07-13 1993-05-12 Compounds and methods for the treatment of inflammatory and immune disorders
US08/062391 1993-05-12
PCT/US1993/006575 WO1994001430A1 (en) 1992-07-13 1993-07-13 2,5-diaryl tetrahydro-thiophenes, -furans and analogs for the treatment of inflammatory and immune disorders

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