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    • 3. 发明申请
    • LEUKOTRIENE B4 DERIVATIVES, METHODS OF PREPARING THEM AND THEIR USE AS DRUGS
    • 新白三烯B4衍生物,用于生产及其作为药物
    • WO1995020562A1
    • 1995-08-03
    • PCT/EP1994000214
    • 1994-01-27
    • SCHERING AKTIENGESELLSCHAFTSKUBALLA, WernerBUCHMANN, BerndHEINDL, JosefFRÖHLICH, WolfgangEKERDT, RolandGIESEN, Claudia
    • SCHERING AKTIENGESELLSCHAFT
    • C07C59/46
    • C07F9/4018C07C59/46C07C59/54C07C69/007C07C69/732C07C235/30C07C405/0066C07C2601/04C07C2601/14C07D309/30C07F9/4015
    • The invention concerns leukotriene B4 derivatives of the formula (I), in which R1 is CH2OH, CH3, CF3, COOR5, CONR6R7, or R1 together with R2 is a carbonyl group, R2 and R3, which may be the same or different, are H or an organic-acid group with 1 to 15 C-atomes, R4 is H, a C1-C14 alkyl group, optionally with one or more substituents, a C3-C10 cycloalkyl group, a C6-C10 aryl group optionally substituted, independently of each other, with one or more halogen, phenyl, C1-C4 alkyl, C1-C4 alkoxy, fluoromethyl, chloromethyl, trifluoromethyl, carboxyl oder hydroxy groups or R4 is a 5- or 6-membered aromatic heterocyclic ring with at least one hetero atom, R5 is H, C1-C10 alkyl, C3-C10 cycloalkyl, a C6-C10 aryl group optionally substituted with 1 to 3 halogen, phenyl, C1-C4 alkyl, C1-C4 alkoxy, fluoromethyl, chloromethyl, trifluoromethyl, carboxyl or hydroxy groups or R5 is CH2-CO-(C6-C10 aryl) or a 5- to 6-membered ring with at least one hetero atom, A is a trans, trans-CH=CH-CH=CH, a -CH2CH2-CH=CH- or a tetramethylene group, B is a straight-chain or branched-chain C1-C10 alkylene group, which may be substituted with fluorine, or the group (a), D is a direct bond, oxygen, sulphur, -C=C-, -CH=CR8, or together with B, may also form a direct bond, R6 and R7, which may be the same or different, are H or C1-C4 alkyl, or R is H and R is C1-C15 alkanoyl or C1-C10 alkane sulphonyl, optionally substituted with OH, R8 is H, C1-C5 alkyl, chlorine, bromine and n is 2 to 5 plus, when R5 is hydrogen, salts of these compounds with physiologically tolerated bases, as well as their cyclodextrin clathrates.
    • 本发明涉及其中R 1 CH 2 OH,CH 3,CF 3,COOR 5,CONR 6 R 7,或R 1与R 2一起表示羰基,R 2和R 3是相同或不同的H或有机残基与1-15的式(I)的白三烯B4衍生物 表示碳原子,R 4是H,任选地单取代或多取代的C1-C14烷基,C3-C10环烷基,任选独立地被取代地被卤素,苯基,C1-C4烷基,C1-C4烷氧基,氟甲基一次或多次 氯甲基,三氟甲基,羧基或羟基取代的C 6 -C 10芳基或具有至少1个杂原子象征着的5-6元芳族杂环,R 5是氢,C1-C10烷基,C3-C10环烷基,任选被1-3个卤素取代的,苯基, 指C1-C4烷基,C1-C4烷氧基,氟甲基,氯甲基,三氟甲基,羧基或羟基取代的C 6 -C 10 - 芳基,CH 2 -CO-(C6-C10)芳基或具有至少1个杂原子的5-6元环 中,是反式,反式CH = CH-CH = CH,一-C H2CH2-CH = CH-或四亚甲基,B是直链或支链C,其可任选被氟取代的1〜10的亚烷基,或(a)象征团,D是一个直接键,氧,硫,-C = C- ,-CH = CR 8,或连同B也可以表示直接键合,R 6和R 7相同或不同并且是H或C1-C4烷基,或者R <7>为H,R <6> C1-C15烷酰基或C1 C10链烷磺酰基代表任选被OH取代,R8是H,C1-C5烷基,氯,溴,n是2-5和,当R 5是氢,其与生理学上可接受的碱及其环糊精笼形物的盐。