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290 条记录 (耗时 0.017 秒)

    Process for the preparation of optically pure aminophenylthio- and aminoaphthalenylthio-propanoic acids
    91.
    发明公开
    Process for the preparation of optically pure aminophenylthio- and aminoaphthalenylthio-propanoic acids 失效
    制备光学纯氨基苯乙酸和氨基十二烷基丙酸的方法

    公开(公告)号：EP0343474A3

    公开(公告)日：1991-01-23

    申请号：EP89108686.0

    申请日：1989-05-13

    申请人： F. HOFFMANN-LA ROCHE AG

    发明人： Coffen, David Llewellyn ,  Madan, Pradeep Balkrishna ,  Schwartz, Alan

    IPC分类号： C07D281/10 ,  A61K31/55 ,  C07C149/42 ,  C07D307/24

    CPC分类号： C07D281/08 ,  C07C319/20 ,  C07C2601/14 ,  C07D281/10 ,  C07C323/56

    摘要： A process for preparing an acid of the general formula
    wherein R₁ and R₂ are each, independently, hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro or R₁ and R₂, taken together with the benzene ring to which they are attached, are naphthalene and Ar is phenyl which is unsubstituted or substituted by one to three substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms and halogen,
    by hydrolyzing a compound of the formula The compounds of formula I formed by the process of the invention are useful in the production of thiazepin-4(5H)-ones of the formula
    and anaogs thereof which have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure and as agents for treating ischemia.

    摘要翻译： 一种制备通式为CHEM的酸的方法，其中R 1和R 2各自独立地为氢，1至4个碳原子的烷基，1至4个碳原子的烷氧基，卤素，三氟甲基或硝基或R 1和R 2， 与它们所连接的苯环一起为萘，Ar为未取代或被一至三个选自1至4个碳原子的烷基，1至4个碳原子的烷氧基和1至4个碳原子的烷氧基取代的苯基，以及 卤素，通过水解式CHEM的化合物通过本发明的方法形成的式I化合物可用于制备具有式（CHEM）的硫杂环丁-4（5H） - 酮和其活性的其它 作为钙通道阻滞剂，因此可用作降低血压的药剂和用作治疗缺血的药剂。

    Leukotriene antagonist prodrugs
    93.
    发明公开
    Leukotriene antagonist prodrugs 失效
    白三烯拮抗剂前体药物

    公开(公告)号：EP0365149A3

    公开(公告)日：1990-07-25

    申请号：EP89309643.8

    申请日：1989-09-21

    申请人： SMITHKLINE BEECHAM CORPORATION

    发明人： Gleason, John Gerald ,  Newton, John Frederick ,  Smallheer, Joanne ,  Hall, Ralph Floyd ,  Phipps, Kathleen A.

    IPC分类号： C07C323/56 ,  C07C323/60 ,  C07C323/66 ,  C07C323/67 ,  C07D233/84 ,  C07D257/04 ,  A61K31/19

    CPC分类号： C07D257/04 ,  A61K31/19 ,  C07C45/298 ,  C07C45/44 ,  C07C45/56 ,  C07C45/62 ,  C07C45/673 ,  C07C45/68 ,  C07C45/71 ,  C07C47/542 ,  C07C47/546 ,  C07C47/548 ,  C07C47/55 ,  C07C47/575 ,  C07C255/33 ,  C07C323/56 ,  C07C323/60 ,  C07C323/66 ,  C07C323/67 ,  C07D233/84 ,  C07D233/90 ,  C07D303/40 ,  C07D303/48 ,  C07D307/38 ,  C07D307/54 ,  C07D309/30

    摘要： A compound represented by the following structural formula (I):
    wherein (a) R₁ is C₈ to C₁₃ alkyl, C₇ to C₁₂ alkoxy, C₇ to C₁₂ alkylthio, C₁₀ to C₁₂ 1-alkynyl, 10-undecynyloxy, 11-­dodecynyl, phenyl-C₄ to C₁₀ alkyl, phenyl-C₃ to C₉ alkoxy, phenylthio-C₃ to C₉ alkyl with the phenyl optionally mono substituted with bromo, chloro, trifluoromethyl, alkoxy, methylthio or trifluoromethylthio, thienyl-C₄ to C₁₀ alkyl furyl-C₄ to C₁₀ alkyl,trifluoromethyl-C₇ to C₁₂ alkyl or cycloheyl-C₄ to C₁₀ alkyl; and
        R₂ is hydrogen, bromo, chloro, methyl, trifluoromethyl, hydroxy, alkoxy or nitro; (b) or R₁ is hydrogen and R₂ is C₈ to C₁₃ alkyl, C₇ to C₁₂ alkoxy, C₇ to C₁₂ alkylthio, C₁₀ to C₁₂ 1-alkynyl, 10-­undecynyloxy, 11-dodecynyl, phenyl-C₄ to C₁₀ alkyl, phenyl-C₃ to C₉ alkoxy, phenylthio-C₃ to C₉ alkyl with the phenyl optionally mono substituted with bromo, chloro, trifluoro­methyl, alkoxy, methylthio or trifluoromethylthio, furyl-C₄ to C₁₀ alkyl, trifluoromethyl-C₇ to C₁₂ alkyl or cyclohexyl-C₄ to C₁₀ alkyl;
        q is 0, 1, or 2;
        Y is COR₃, CH(R₄)(CH₂) m COR₃ or CH(R₄)(CH₂) m -­tetrazol-5-yl the tetrazol-5-yl being unsubstituted or substituted with A;     R₁₆ and R₁₇ are independently hydrogen or C₁₋₄ alkyl;
        j is 0 to 6;     R₁₈ is hydrogen, alkyl, COR₃, SO₃H, SO₂NH₂, COCH₂OH or CHOHCH₂OH;
        R₃ is amino, (CH₂) n CO₂CH₂CONR₁₆R₁₇, or OR₁₄;
        R₁₄ is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, alkylarylalkyl, alkyl substituted amino or alkylamino, - OCH₂CONR₇R₈, indanyl, pivaloyloxymethyl, acetoxymethyl, propionyloxymethyl, glycyloxymethyl, phenylglycyloxymethyl, or thienylglycyloxymethyl;
        R₄ is hydrogen, methyl, alkoxy, fluoro or hydroxy;
        m is 0, or 1;
        R is (CH₂) n COR₆, CH(CO₂H)CH₂COR₆, (CH₂) n CO₂CH₂CONR₁₆,R₁₇, or an imidazole of the formula     n is 0 to 6;
        R₅ is hydrogen, amino, or NHCOCH₂CH₂CH(NH₂)CO₂H;
        R₆ is amino, NH(CH₂) n CO₂H, SO₃H, SO₂NH₂, CN, tetrazol-5-yl unsubstituted or substituted with A as defined above, or OR₁₅;
        R₇ is hydrogen, alkyl or alkenyl;
        R₈ is hydrogen, alkyl, carboxyl or carboxamido, or,
    when R₇ and R₉ are hydrogen or alkyl, (CH₂) m COOR₁₅;
        R₉ is hydrogen, alkyl or (CH₂) m COOR₁₅;
        R₁₅ is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, alkylarylalkyl, allayl substituted amino or alkylamino, -OCH₂CONR₇R₈, indanyl, pivaloyloxymethyl, acetoxymethyl, propionyloxymethyl, glycyloxymethyl, phenylglycyloxymethyl, or thienylglycyloxymethyl;
        provided that 1) when n is 0, R₅ is hydrogen, 2) R₇, R₈ and R₉ are not all hydrogen, 3) any of R₁and R₂ above are not alkylthio or phenylthioalkyl when q is 1 or 2, 4) R₃ and R₆ are not both hydroxy, 5) OR₁₄ and OR₁₅ are not simultaneously hydroxy; 6) if R₄ is hydroxy and m is 0, R₁₄ is hydrogen; or
        a pharmaceutically acceptable salt thereof.

    摘要翻译： 由下列结构式（Ⅰ）表示的化合物：其中（a）R 1是C 8 -C 13烷基，C 8 -C 12烷氧基，C 8 -C 12烷硫基，C 10 -C 12 1-炔基， 苯基-C3-C8烷氧基，苯基硫基-C3-C8烷基，其中苯基任选地被溴，氯，三氟甲基，烷氧基，甲硫基或三氟甲硫基取代，噻吩基-C4-C10烷基呋喃基-C4-C10烷基， 三氟甲基-C 8至C 12烷基或环
    己基-C 4至C 10烷基; 和R 2是氢，溴，氯，甲基，三氟甲基，羟基，烷氧基或硝基; （b）或R 1是氢和R 2是C 8 -C 13烷基，C 8 -C 12烷氧基，C 8 -C 12烷硫基，C 10 -C 12 1-炔基，10-十一碳炔氧基，11-十二炔基，苯基-C 4 -C 10烷基， 任选地被溴，氯，三氟甲基，烷氧基，甲硫基或三氟甲硫基，呋喃基-C 4至C 10烷基，三氟甲基-C 8至C 12烷基或环己基-C 4至C 10烷基取代的苯基;苯基硫基-C 3至C 8烷基; q是0,1或2; Y是COR 3，CH（R 4）（CH 2）mCOR 3或CH（R 4）（CH 2）m-四唑-5-基，四唑-5-基未被取代或被A取代; R 16和R 18独立地是氢或C 1-4烷基; j是0至6; R 17是氢，烷​​基，COR 3，SO 3 H，SO 2 NH 2，COCH 2 OH或CHOHCH 2 OH; R 3是氨基，（CH 2）n CO 2 CH 2 CONR 16 R 17或OR 14; 烷基，烷基芳基，烷基芳基烷基，烷基取代的氨基或烷基氨基，-OCH 2 CONR 8 R 9，茚满基，新戊酰氧基甲基，乙酰氧基甲基，丙酰氧基甲基，甘氨酰氧甲基，苯基甘氨酰氧甲基或噻吩基甘氨酰氧甲基; R 4是氢，甲基，烷氧基，氟或羟基; m是0或1; R是（CH 2）n COR 6，CH（CO 2 H）CH 2 COR 6，（CH 2）n CO 2 CH 2 CONR 16，R 17或式n的咪唑是0-6; R 5是氢，氨基或NHCOCH 2 CH 2 CH（NH 2）CO 2 H; R 6为氨基，NH（CH 2）n CO 2 H，SO 3 H，SO 2 NH 2，CN，未被取代或被上述定义的A取代的四唑-5-基或OR 15; R 7是氢，烷​​基或链烯基; R 7是氢，烷​​基，羧基或甲酰氨基，或当R 7和R 7是氢或烷基时，（CH 2）m COOR 15; R 8是氢，烷基或（CH 2）m COOR 15; 烷基，环烷基，芳基，芳基烷基，烷基芳基，烷基芳基烷基，烯丙基取代的氨基或烷基氨基，-OCH 2 CONR 8 R 9，茚满基，新戊酰氧基甲基，乙酰氧基甲基，丙酰氧基甲基， 条件是1）当n是0时，R 5是氢，2）R 6，R 7和R 7不全是氢，3）当q是1或2,4时，上述R 1和R 2中的任何一个都不是烷硫基或苯硫基烷基，R 3和R 6是 不是两个羟基，5）OR 14和OR 15不同时是羟基; 6）如果R 4是羟基并且m是0，R 14是氢; 或其药学上可接受的盐。

    Process for the preparation of intermediates for the synthesis of diltiazem
    95.
    发明公开
    Process for the preparation of intermediates for the synthesis of diltiazem 失效
    一种用于制备中的中间体的对地尔硫的合成过程。

    公开(公告)号：EP0353538A2

    公开(公告)日：1990-02-07

    申请号：EP89113135.1

    申请日：1989-07-18

    申请人： ZAMBON GROUP S.p.A.

    发明人： Giordano, Claudio ,  Merli, Valeriano ,  Sagramora, Giorgio ,  Soriato, Giorgio

    IPC分类号： C07C323/36 ,  C07C319/28 ,  C07B57/00

    CPC分类号： C07C319/28 ,  C07C323/56

    摘要： A process for the preparation of (2S,3S)-threo-2-hydroxy-3-(2-­aminophenylthio)-3-(4-methoxyphenyl)-propionic acid by resolution of the racemic mixture is described.
    The resolution is carried out by using as resolving agent (1S,2S)­-threo-1-phenyl-2-amino-1,3-propanediol or (1S,2S)-threo-1-(4-­methylthiophenyl)-2-amino-1,3-propanediol.

    摘要翻译： 描述了用于（2S，3S）的制备苏-2-羟基-3-（2aminophenylthio）一种方法-3-（4-甲氧基苯基）通过拆分外消旋混合物丙离子酸。 分辨率是通过使用作为拆解剂（1S，2S）中进行 - 苏-1-苯基-2-氨基-1,3-丙二醇或（1S，2S） - 苏1-（4-甲硫基苯基）-2- 氨基-1,3-丙二醇。

    Process for the preparation of optically pure aminophenylthio- and aminoaphthalenylthio-propanoic acids
    96.
    发明公开
    Process for the preparation of optically pure aminophenylthio- and aminoaphthalenylthio-propanoic acids 失效
    一种制备的纯Aminophenylthio-和Aminonaphthalenylthio - 丙酸与光学活性的过程。

    公开(公告)号：EP0343474A2

    公开(公告)日：1989-11-29

    申请号：EP89108686.0

    申请日：1989-05-13

    申请人： F. HOFFMANN-LA ROCHE AG

    发明人： Coffen, David Llewellyn ,  Madan, Pradeep Balkrishna ,  Schwartz, Alan

    IPC分类号： C07D281/10 ,  A61K31/55 ,  C07C149/42 ,  C07D307/24

    CPC分类号： C07D281/08 ,  C07C319/20 ,  C07C2601/14 ,  C07D281/10 ,  C07C323/56

    摘要： A process for preparing an acid of the general formula
    wherein R₁ and R₂ are each, independently, hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro or R₁ and R₂, taken together with the benzene ring to which they are attached, are naphthalene and Ar is phenyl which is unsubstituted or substituted by one to three substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms and halogen,
    by hydrolyzing a compound of the formula

    The compounds of formula I formed by the process of the invention are useful in the production of thiazepin-4(5H)-ones of the formula
    and anaogs thereof which have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure and as agents for treating ischemia.

    摘要翻译： 一种用于制备通式 worin R1和R2的酸处理是1至4个碳原子的每一个，unabhängig，氢，烷基，烷氧基的1至4个碳原子的卤素，三氟甲基或硝基，或R 1和R 2， 与苯环合在一起时它们所连接，是萘和Ar是苯基所有这些是由选自1烷基的选择，以4个碳原子的一个至三个取代基，烷氧基的1至4个碳原子和unsubstituiertem或substituiertem 卤素，通过水解式I化合物予通过本发明的方法形成的式I的化合物在生产硫杂氮杂-4（5H）式 - 酮的有用和它们的哪个anaogs具有活性 作为钙通道阻断剂，因此是作为用于降低血压和作为用于治疗局部缺血剂剂。

    2-Hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid, 8'-phenylmenthyl ester, especially for diltiazem
    97.
    发明公开
    2-Hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid, 8'-phenylmenthyl ester, especially for diltiazem 失效
    2-羟基-3-（4-甲氧基苯基）-3-（2-氨基苯硫基）丙酸-8'-苯基酯，地塞米松。

    公开(公告)号：EP0342904A2

    公开(公告)日：1989-11-23

    申请号：EP89304895.9

    申请日：1989-05-15

    申请人： MARION LABORATORIES, INC. (a Delaware corporation)

    发明人： Palmer, James T.

    IPC分类号： C07D281/10 ,  A61K31/55 ,  C07C149/42

    CPC分类号： C07C323/56 ,  C07C319/14 ,  C07D281/10

    摘要： A method comprising steps of, first, contacting 4-methoxybenzaldehyde with a chloroacetic acid, (*)-8-phenylmenthyl ester, second, contacting the product from the first step with 2-aminothiophenol, by steps under conditions such that a (2*,3*)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid, (*)-8'-phenylmentthyl ester is prepared, third, hydrolyzing said propionic acid ester with an alkaline hydrolyzing agent, and fourth, contacting the product from the third step with an acid, by steps under conditions such that a (2*,3*)-2-hydroxy-3(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid is prepared. Optically active forms of the title compound are also claimed.

    摘要翻译： 一种方法，包括以下步骤：首先使4-甲氧基苯甲醛与氯乙酸（*） - 8-苯基甲酯接触，其次，使第一步产物与2-氨基苯硫酚接触，步骤使得（2 * ，3 *） - 2-羟基-3-（4-甲氧基苯基）-3-（2-氨基苯硫基）丙酸，（*） - 8'-苯基乙基酯，第三，用碱性水解水解所述丙酸酯 并且第四步，使得（2 *，3 *）-2-羟基-3（4-甲氧基苯基）-3-（2-氨基苯硫基）丙酸 制备酸。 还要求保护标题化合物的光学活性。