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    • 1. 发明授权
    • 2-bicyclobenzimidazoles, processes for their preparation and medicaments
containing these compounds
    • 2-二环苯并咪唑,它们的制备方法和含有这些化合物的药物
    • US5414088A
    • 1995-05-09
    • US847060
    • 1992-04-14
    • Wolfgang Von Der SaalHarald ZilchErwin Bohm
    • Wolfgang Von Der SaalHarald ZilchErwin Bohm
    • A61K31/415A61K31/47A61P7/02C07D401/04C07D403/04C07D487/04C07D215/227C07D235/18
    • C07D401/04C07D403/04C07D487/04
    • The invention concerns compounds of formula I ##STR1## where R.sup.1 is hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.3 -C.sub.7 -cycloalkyl, R.sup.2 is C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, cyano, carboxy [carbonyl substituted by hydroxyl], C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy, amino, C.sub.1 -C.sub.6 -alkylamino, di-C.sub.1 -C.sub.6 -alkylamino or hydrazino or R.sup.1 and R.sup.2 together are C.sub.2 -C.sub.6 -alkylidene or C.sub.3 -C.sub.6 -cycloalkylidene or R.sup.1 and R.sup.2, together with the carbon atoms to which they are attached, form a C.sub.3 -C.sub.7 -spirocycle, n is 0 or 1, R.sup.3 is hydrogen, C.sub.1 -C.sub.8 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, C.sub.3 -C.sub.7 -cycloalkyl, benzyl, carboxy-C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyloxycarbonyl-C.sub.1 -C.sub.6 -alkyl or di-C.sub.1 -C.sub.6 -alkyloxophosphinyl-C.sub.1 -C.sub.6 -alkyl and R.sup.4 -R.sup. 6 are as in the specification. These compounds of formula I serve for the preparation of medicaments to inhibit erythrocyte and thrombocyte aggregation. Therefore, these compounds are useful for the treatment of diseases where these aggregations occur such as arterial occlusive or ischaemic conditions, venous insufficiency or diabetes mellitus.
    • PCT No.PCT / EP90 / 01663 Sec。 371日期:1992年4月14日 102(e)日期1992年4月14日PCT 1990年9月4日PCT PCT。 出版物WO91 / 04974 1991年4月18日,本发明涉及式I化合物(Ⅰ)其中R1是氢,C1-C6-烷基,C2-C6-烯基或C3-C7-环烷基,R2是C1-C6-烷基 ,C 2 -C 6 - 烯基,氰基,羧基[被羟基取代的羰基],C 1 -C 6 - 烷基,C 1 -C 6 - 烷氧基,氨基,C 1 -C 6 - 烷基氨基,二-C 1 -C 6烷基氨基或肼基或R 1和R 2 一起是C 2 -C 6亚烷基或C 3 -C 6亚环烷基或R 1和R 2与它们连接的碳原子一起形成C 3 -C 7 - 螺环,n是0或1,R 3是氢,C 1 -C 8 - 烷基,C 2 -C 6 - 烯基,C 2 -C 6 - 炔基,C 3 -C 7 - 环烷基,苄基,羧基-C 1 -C 6 - 烷基,C 1 -C 6 - 烷氧基羰基-C 1 -C 6烷基或二-C 1 -C 6烷氧基氧膦 -C 1 -C 6烷基和R 4 -R 6如说明书中所述。 这些式I化合物用于制备抑制红细胞和血小板聚集的药物。 因此,这些化合物可用于治疗发生这些聚集的疾病,例如动脉闭塞或缺血性疾病,静脉功能不全或糖尿病。
    • 5. 发明授权
    • Process for the production of asymmetrical phosphoric acid diesters
    • 生产不对称磷酸二酯的方法
    • US5734042A
    • 1998-03-31
    • US682571
    • 1996-07-29
    • Einhard KiegelHarald Zilch
    • Einhard KiegelHarald Zilch
    • C07H19/06C07F9/09C07F9/6558C07F9/6561C07H19/10C07H19/20C07H1/02C07H19/207
    • C07H19/10C07F9/09C07H19/20
    • The present invention concerns a process for the production of asymmetrical phosphoric acid diesters. The process is characterized in that a phosphoric acid ester is condensed with a compound containing hydroxy groups in the presence of an arylsulfonic acid chloride and an organic base, the residue of evaporation is stirred out with an organic solvent after the hydrolysis, the arylsulfonic acid pyridine salt which forms is nearly completely crystallized and recycled, the lipid derivative that is formed is precipitated as a sparingly soluble salt by addition of a solution containing alkaline-earth ions and isolated, the sparingly soluble salt is isolated as the free acid in an organic solvent by suspension in a water-immiscible organic solvent and a dilute aqueous mineral acid, the crude product is purified if desired, by means of preparative chromatography on a RP phase and subsequently the free acid is converted if desired into any desired salt.
    • PCT No.PCT / EP95 / 00219 Sec。 371日期:1996年7月29日 102(e)日期1996年7月29日PCT提交1995年1月21日PCT公布。 公开号WO95 / 20596 日期1995年8月3日本发明涉及不对称磷酸二酯的制造方法。 该方法的特征在于,在芳基磺酰氯和有机碱的存在下,将磷酸酯与含有羟基的化合物缩合,水解后用有机溶剂搅拌残余物,芳基磺酸吡啶 形成的盐几乎完全结晶并再循环,所形成的脂质衍生物通过加入含有碱土离子的溶液并分离而作为微溶盐沉淀,将微溶盐作为游离酸在有机溶剂中分离 通过悬浮在与水不混溶的有机溶剂和稀无机酸水溶液中,如果需要,通过RP相上的制备色谱法纯化粗产物,随后如果需要将游离酸转化成任何所需的盐。
    • 6. 发明授权
    • Tricyclic thiazole and oxazole derivatives and pharmaceutical agents
containing them
    • 三环噻唑和恶唑衍生物和含有它们的药剂
    • US5512564A
    • 1996-04-30
    • US193056
    • 1994-03-04
    • Harald ZilchHerbert LeinertAlfred Mertens
    • Harald ZilchHerbert LeinertAlfred Mertens
    • A61K31/425A61K31/44C07D498/14C07D513/14C07D519/00
    • C07D513/14
    • The present invention concerns thiazolo- 2,3-a!pyrrole and oxazolo- 1,2-a!pyrrole derivatives of formula I ##STR1## in which HET represents a heterocyclic ring with 3-7 ring atoms which can be substituted by one, two or three residues R.sup.1 which can be the same or different,Y represents an oxygen or sulphur atom, or a SO or SO.sub.2 group,X can be an oxygen or sulphur atom,R denotes an aliphatic residue with 1-9 C-atoms which can be substituted by phenyl or denotes a phenyl ring or a carbocyclic ring with 7-15 C atoms or a heterocyclic ring system each having 5 or 6 ring atoms,in which the aforementioned phenyl rings, carbocyclic rings or heterocyclic ring system can be substituted once or several times, if desired, and R1-R5 denote hydrogen or an aliphatic residue, as well as their tautomers, enantiomers, diastereomers and physiologically tolerated salts.
    • PCT No.PCT / EP92 / 02015 Sec。 371日期1994年3月4日 102(e)1994年3月4日PCT PCT 1992年9月2日PCT公布。 公开号WO93 / 05047 日本1993年3月18日。本发明涉及式I的噻唑并[2,3-a]吡咯和恶唑并[1,2-a]吡咯衍生物,其中HET表示具有 3-7个可被一个,两个或三个可以相同或不同的残基R1取代的环原子,Y代表氧或硫原子,或SO或SO2基团,X可以是氧或硫原子,R 表示具有1-9个C原子的脂族残基,其可以被苯基取代,或表示苯环或具有7-15个C原子的碳环或每个具有5或6个环原子的杂环系统,其中上述苯基 如果需要,环,碳环或杂环系统可以被取代一次或数次,并且R 1 -R 5表示氢或脂族残基,以及它们的互变异构体,对映异构体,非对映异构体和生理上耐受的盐。
    • 7. 发明授权
    • Specific lipid conjugates to nucleoside diphosphates and their use as drugs
    • 特异性脂质偶联物与核苷二磷酸及其作为药物的用途
    • US06372725B1
    • 2002-04-16
    • US09204497
    • 1998-12-04
    • Harald ZilchDieter Herrmann
    • Harald ZilchDieter Herrmann
    • A61K3170
    • C07H19/10C07H19/207
    • The present invention concerns new phospholipid derivatives of nucleosides of the general formula (I) in which R1 represents a straight-chained or branched, saturated or unsaturated aliphatic residue with 9-14 carbon atoms which can optionally be substituted once or several times; R2 can represent a straight-chained or branched, saturated or unsaturated aliphatic residue with 8-12 carbon atoms which can optionally be substituted once or several times; m is 2 or 3; A can represent a methylene group or an oxygen; Nuc can be a nucleoside or a residue derived from a nucleoside derivative; and tautomers thereof and their physiologically tolerated salts of inorganic and organic acids and bases as well as pharmaceutical preparations containing these compounds.
    • 本发明涉及通式(I)的核苷的新型磷脂衍生物,其中R 1表示具有9-14个碳原子的直链或支链,饱和或不饱和的脂肪族残基,其可任选被取代一次或数次; R2可以表示具有8-12个碳原子的直链或支链,饱和或不饱和的脂肪族残基,其可任选被取代一次或数次; m为2或3; A可以表示亚甲基或氧; Nuc可以是衍生自核苷衍生物的核苷或残基; 及其互变异构体及其生理上耐受的无机和有机酸和碱的盐以及含有这些化合物的药物制剂。
    • 9. 发明授权
    • Purine analog nucleoside and nucleotide compounds
    • 嘌呤类似物核苷和核苷酸化合物
    • US5446139A
    • 1995-08-29
    • US809506
    • 1992-02-21
    • Frank SeelaWerner BourgeouisRainer GumbiowskiAngelika RolingHelmut RosemeyerAlfred MertensHarald ZilchBernhard KonigEdith Koch
    • Frank SeelaWerner BourgeouisRainer GumbiowskiAngelika RolingHelmut RosemeyerAlfred MertensHarald ZilchBernhard KonigEdith Koch
    • A61K31/40A61K31/435A61K31/505A61K31/53A61K31/70A61K31/7042A61K31/7052A61P31/12C07D405/04C07D471/04C07D487/04C07F9/09C07F9/6561C07H19/04C12Q1/68C07H19/16
    • C07H19/04
    • The invention concerns nucleoside derivatives of the formula I ##STR1## in which Ba signifies an indolyl (A), benzimidazolyl (B), pyrrolopyridinyl (C), imidazopyridinyl (D), triazolopyrimidinyl (E), imidazotriazinyl (F) or imidazopyrimidinyl (G) group substituted by R.sup.1, R.sup.2 and R.sup.3, in which R.sup.1, R.sup.2 and R.sup.3, which can be the same or different, signify hydrogen, halogen, a C.sub.1 -C.sub.7 -alkyl, C.sub.2 -C.sub.7 -alkenyl, hydroxy, mercapto, C.sub.1 -C.sub.7 -alkylthio, C.sub.1 -C.sub.7 -alkoxy, C.sub.2 -C.sub.7 -alkenyloxy, ar-C.sub.1 -C.sub.5 -alkyl, ar-C.sub.2 -C.sub.5 -alkenyl, ar-C.sub.1 -C.sub.5 -alkoxy, ar-C.sub.2 -C.sub.5 -alkenyloxy, aryloxy, nitro, amino-C.sub.1 -C.sub.7 -alkyl, C.sub.1 -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl, di-C.sub.1 -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl, amino, a substituted amino group --NMR.sup.4 or --N(R.sup.4).sub.2 or an imino group --N.dbd.CH--R.sup.4, and R.sup.4 has the meaning given in the description, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each signify hydrogen or one or two of the radicals R.sup.5, R.sup.6, R.sup.7 and R.sup.8 a hydroxyl, halogen, cyano, azido or a substituted amino group --NHR.sup.4 or --N(R.sup.4).sub.2 or R.sup.5 and R.sup.7 can together represent a further bond between C-2' and C-3' and Y represents hydrogen or a C.sub.1 -C.sub.7 -alkylcarbonyl, monophosphate, diphosphate or triphosphate group, whereby "aryl" signifies a phenyl or naphthyl group and "hetaryl" a furanyl, thienyl or pyridyl group, as well as their possible anomers, N.sup.7 - or N.sup.9 -regioisomers (purine nomenclature), tautomers and salts.
    • PCT No.PCT / EP90 / 00650 Sec。 一九九二年二月二十一日 102(e)日期1992年2月21日PCT提交1990年4月23日PCT公布。 第WO91 / 01325号公报 1991年2月7日,本发明涉及式Ⅰ(I)的核苷衍生物,其中Ba表示吲哚基(A),苯并咪唑基(B),吡咯并吡啶基(C),咪唑并吡啶基(D),三唑并嘧啶基(E ),被R1,R2和R3取代的咪唑并吡嗪基(F)或咪唑并嘧啶基(G)基团,其中可以相同或不同的R 1,R 2和R 3表示氢,卤素,C 1 -C 7 - 烷基, C7-烯基,羟基,巯基,C1-C7-烷硫基,C1-C7-烷氧基,C2-C7-烯氧基,芳基-C1-C5-烷基,ar-C2-C5-烯基,ar-C1-C5-烷氧基, 芳基氧基,硝基,氨基-C 1 -C 7 - 烷基,C 1 -C 7 - 烷基氨基-C 1 -C 7 - 烷基,二-C 1 -C 7 - 烷基氨基-C 1 -C 7 - 烷基,氨基,取代的 氨基-NMR4或-N(R4)2或亚氨基-N = CH-R4,R4具有说明书中给出的含义,R5,R6,R7和R8各自表示氢或一个或两个基团R 5 ,R6,R7和R8是羟基,卤素,氰基,叠氮基或取代的氨基-NHR4或-N(R4)2或R5和R7可以一起代表另一个b C-2'和C-3'之间,Y表示氢或C1-C7-烷基羰基,一磷酸,二磷酸或三磷酸基,其中“芳基”表示苯基或萘基,“杂芳基”是呋喃基,噻吩基或吡啶基 组,以及它们可能的端基异构体,N7-或N9-区域异构体(嘌呤命名法),互变异构体和盐。