No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds
    4.
    发明申请
    No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds 有权
    无载体添加的亲核[F-18]芳香族化合物的氟化

    公开(公告)号:US20120123120A1

    公开(公告)日:2012-05-17

    申请号:US13263333

    申请日:2010-04-01

    摘要: Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

    摘要翻译: 显示了用芳族亲核取代反应的前体作为芳族环上的给电子基团和吸电子基团取代的苯基碘鎓衍生物衍生物。 碘鎓叶立德基团被诸如卤素离子的亲核试剂取代,得到相应的卤代芳基衍生物。 无载体添加的[F-18]氟化物离子专门代替这些衍生物中的碘鎓内鎓盐部分,并提供高比活性F-18标记的氟衍生物。 已经合成了保护的左旋多巴-6-碘鎓叶立德衍生物作为制备无载体添加的6- [F-18]氟-L-多巴的前体。 该L-多巴胺衍生物中的碘鎓叶立德碱通过无载体添加的[F-18]氟离子被亲核取代,得到[F-18]氟中间体,其在酸水解时产生6- [F-18]氟 -L-多巴

    1,3-dihydro-2H-imidazol-2-one compounds
    9.
    发明授权
    1,3-dihydro-2H-imidazol-2-one compounds 失效
    1,3-二氢-2H-咪唑-2-酮化合物

    公开(公告)号:US5869515A

    公开(公告)日:1999-02-09

    申请号:US930478

    申请日:1997-09-29

    摘要: The present invention concerns the compounds of formula ##STR1## the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R.sup.1 and R.sup.2 each independently are hydrogen; C.sub.1-6 alkyl; difluoromethyl; trifluoromethyl; C.sub.3-6 cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo�2.2.1!-2-heptenyl; bicyclo�2.2.1!heptanyl; C.sub.1-6 alkylsulfonyl; arylsulfonyl; or substituted C.sub.1-10 alkyl; R3 is hydrogen, halo or C.sub.1-6 alkyloxy ##STR2## is a bivalent radical of formula ##STR3## Alk is C1-4alkanediyl; --A--B-- is a bivalent radical of formula: --CR.sup.6 .dbd.CR.sup.7 -- or --CHR.sup.6 --CHR.sup.7 --; L is hydrogen; optionally substituted C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkyloxycarbonyl; optionally substituted C.sub.3-6 alkenyl; optionally substituted piperidinyl; C.sub.1-6 alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het.sup.1 is morpholinyl or optionally substituted pyridinyl, -furanyl, -thienyl, -hydroxypyridinyl, -imidazolyl, -thiazolyl, -oxazolyl, -isoquinolinyl, -quinolinonyl, -piperidinyl, -piperazinyl; and Het.sup.2 is morpholinyl or optionally substituted piperidinyl, -piperazinyl, -pyridinyl, -furanyl or -thienyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.

    摘要翻译: PCT No.PCT / EP96 / 01393 Sec。 371日期:1997年9月29日 102(e)1997年9月29日PCT PCT 1996年3月28日PCT公布。 公开号WO96 / 31487 日期:1996年10月10日本发明涉及式(I)的化合物:(I)N-氧化物形式,其药学上可接受的酸或碱加成盐及其立体化学异构形式,其中R1和R2各自独立地为氢; C 1-6烷基; 二氟甲基 三氟甲基 C 3-6环烷基; 含有一个或两个选自氧,硫或氮的杂原子的饱和的5-,6-或7-元杂环; 茚满基 双环[2.2.1] -2-庚烯基; 双环[2.2.1]庚基; C 1-6烷基磺酰基; 芳基磺酰基; 或取代的C 1-10烷基; R 3是氢,卤素或C 1-6烷氧基,是下式的二价基团:其中A k是C 1-4烷二基; -A-B-是下式的二价基团:-CR 6 = CR 7 - 或-CHR 6 -CHR 7 - ; L是氢; 任选取代的C 1-6烷基; C 1-6烷基羰基; C 1-6烷氧基羰基; 任选取代的C 3-6烯基; 任选取代的哌啶基; C 1-6烷基磺酰基或芳基磺酰基; 芳基是任选取代的苯基; - Het1是吗啉基或任意取代的吡啶基, - 呋喃基, - 噻吩基, - 羟基吡啶基, - 咪唑基, - 噻唑基, - 恶唑基, - 异喹啉基, - 喹啉酮基, - 哌啶基, 和Het2是吗啉基或任选取代的哌啶基,哌嗪基, - 吡啶基, - 呋喃基或 - 噻吩基; 具有PDE IV和细胞因子抑制活性。 本发明还涉及制备式(I)化合物及其药物组合物的方法。