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    AZINYLOXY, AND PHENOXY-DIARYL-CARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION AND USE AS MIXED ETA/ETB ENDOTHELIN RECEPTOR ANTAGONISTS
    19.
    发明申请
    AZINYLOXY, AND PHENOXY-DIARYL-CARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION AND USE AS MIXED ETA/ETB ENDOTHELIN RECEPTOR ANTAGONISTS 审中-公开
    AZINYLOXY-和苯氧基二芳基羧酸衍生物，其制备及其作为混合ETA / ETB内皮素受体拮抗剂

    公开(公告)号：WO1998009953A2

    公开(公告)日：1998-03-12

    申请号：PCT/EP1997004688

    申请日：1997-09-02

    Applicant: BASF AKTIENGESELLSCHAFT ,  AMBERG, Wilhelm ,  JANSEN, Rolf ,  KLING, Andreas ,  KLINGE, Dagmar ,  RIECHERS, Hartmut ,  HERGENRÖDER, Stefan ,  RASCHACK, Manfred ,  UNGER, Liliane

    Inventor： BASF AKTIENGESELLSCHAFT

    IPC: C07D237/52

    CPC classification number: C07D239/70 ,  C07C59/66 ,  C07C69/734 ,  C07D239/34 ,  C07D239/52 ,  C07D239/60 ,  C07D491/04

    Abstract: Carboxylic acid derivatives have the formula (I), in which R stands for tetrazole or a group (a); R stands for hydrogen, hydroxy, NH2, NH(C1-c4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkinyl, C1-C4-alkyl halide, C1-C4-alkoxy, C1-C4-alkoxy halide or C1-C4-alkylthio, or CR is linked with CR , as indicated below, into a 5- or 6-membered ring; X stands for nitrogen or methine; Y stands for nitrogen or methine; Z stands for nitrogen or CR , wherein R is hydrogen or C1-C4-alkyl or CR forms together with CR or CR an optionally substituted 5- or 6-membered alkylene or alkenylene ring, and wherein one or more methylene groups can be substituted by hydrogen, sulphur, -NH or -N(C1-C4-alkyl); R stands for hydrogen, hydroxy, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkinyl, C1-C4-hydroxyalkyl, C1-C4-alkyl halide, C1-C4-alkoxy, C1-C4-alkoxy halide, C1-C4-alkylthio; or CR is linked to CR as indicated above into a 5- or 6-membered ring, R and R (which may be identical or different) stand for optionally substituted phenyl or naphthyl, or for phenyl or naphthyl which are linked to each other at the ortho-position by a direct bond, a methylene, ethylene or ethenylene group, an oxygen or sulphur atom or an SO2, NH or N-alkyl group; optionally substituted C3-C8-cycloalkyl; R stands for optionally substituted C3-C8-cycloalkyl; optionally substituted phenyl or naphthyl, a 5- or 6-membered, optionally substituted heteroaromatic compound containing one to three nitrogen atoms and/or one sulphur or oxygen atom; W stands for sulphur or oxygen; Q is a spacer with a length that corresponds to a C2-C4 chain. Also disclosed are the physiologically tolerable salts of these compounds, as well as their pure enantiomer and diastereoisomer forms, their preparation and use as mixed ETA/ETB-receptor antagonists.

    Abstract translation: 本发明涉及式（I）式的羧酸衍生物，其中R <1>四唑或基团（a）中，R <2>是氢，羟基，NH 2，NH（C1-C4烷基），N（C1-C4烷基） 2，卤素，C1-C4烷基，C2-C4链烯基，C2-C4炔基，C1-C4卤代烷基，C1-C4烷氧基，C1-C4卤代烷氧基或C1-C4烷硫基，或CR <2 是> CR <10>如下所示，得到的5-或6-元环; X氮或次甲基; ÿ氮或次甲基; <2>或CR <3> Z是氮或CR <10>，其中R <10>是氢或C1-4烷基，或CR <10>与CR 5或6元的亚烷基或亚烯基一起 可以可任选被取代，且其中在每种情况下的一个或由氧，硫，-NH或-N（C1-C4烷基）取代多个亚甲基，取代; [R <3>是氢，羟基，NH 2，NH（C1-C4烷基），N（C1-C4-烷基）2，卤素，C1-C4烷基，C2-C4链烯基，C2-C4炔基，C1 C4羟烷基，C1-C4卤代烷基，C1-C4烷氧基，C1-C4卤代烷氧基，C1-C4烷硫基; 或CR <3>为CR <10>如上所指出的，以形成一个5元或6元环; [R <4>和R <5>（其可以是相同或不同的），苯基或萘基，苯基或萘基，任选被取代，或苯基或萘基，在经由直接键，亚甲基，亚乙基或亚乙烯基邻位 一个氧或硫原子或-SO 2 - ，NH-或N-烷基键合在一起; C3-C8环烷基任选地取代; [R <6>是任选取代的C 3 -C 8 - 环烷基; 苯基或萘基，任选被取代; 五元或六元杂芳族，含一至三个氮原子和/或一个硫或氧原子，并且可任选被取代; W是硫或氧; Q对应于长度为C2-C4链的间隔，意思是，和其生理学上可接受的盐，以及对映体纯的形式和diastereoisomerenreinen; 它们的制备和作为混合ETA / ETB受体拮抗剂使用。

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