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    Mycophenolic acid derivatives in the treatment of rheumatoid arthritis
    1.
    发明授权
    Mycophenolic acid derivatives in the treatment of rheumatoid arthritis 失效
    霉酚酸衍生物治疗类风湿关节炎

    公开(公告)号：US4959387A

    公开(公告)日：1990-09-25

    申请号：US125027

    申请日：1987-11-24

    申请人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui ,  Joseph M. Muchowski

    发明人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui ,  Joseph M. Muchowski

    IPC分类号： C07D307/88

    CPC分类号： C07D307/88

    摘要： A method of treating rheumatoid arthritis which method comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein: A is oxygen or sulfur;R.sup.1 is selected from the group consisting of H, ##STR2## in which Y is oxygen or sulfur:R.sup.2 is alkyl, haloalkyl or --NR.sup.4 R.sup.5, where R.sup.4 and R.sup.5 are independently H, alkyl, haloalkyl, cycloalkyl, phenyl optionally monosubstituted with halogen, hydroxy, carboxy, chlorocarbonyl, nitro, cyano, phenyl, alkyl, acyl, alkoxycarbonyl, acylamino, dialkylamino or dialkylaminoethoxycarbonyl, phenyl optionally disubstituted with hydroxy, carboxy, nitro or alkyl, or benzyl optionally substituted with dialkylamino;n is an integer from 0-6;R.sup.3 is H alkyl or a pharmaceutically acceptable cation;Q and R are independently H or --CO.sub.2 R.sup.3 ; andZ is selected from the group consisting of ##STR3## in which X is oxygen or sulfur,R.sup.7 is H, alkyl, alkenyl, cycloalkyl, optionally substituted phenyl, optionally substituted benzyl or a pharmaceutically acceptable cation; andR.sup.8 and R.sup.9 are independently H, alkyl or cycloalkyl, or R.sup.8 and R.sup.9 taken together are --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 -- or --(CH.sub.2).sub.2 O(CH.sub.2).sub.2 --;with the proviso that R.sup.1 and R.sup.7 cannot both be H if X and A are oxygen.

    摘要翻译： 治疗类风湿性关节炎的方法，该方法包括向需要这种治疗的哺乳动物施用治疗有效量的下式化合物及其药学上可接受的盐，其中：A为氧或硫; R1选自H，其中Y是氧或硫的R 2是烷基，卤代烷基或-NR 4 R 5，其中R 4和R 5独立地是H，烷基，卤代烷基，环烷基，任选被卤素单取代的苯基， 羟基，羧基，氯代羰基，硝基，氰基，苯基，烷基，酰基，烷氧基羰基，酰基氨基，二烷基氨基或二烷基氨基乙氧基羰基，任选被羟基，羧基，硝基或烷基二取代的苯基或任选被二烷基氨基取代的苄基; n是0-6的整数; R3是H烷基或药学上可接受的阳离子; Q和R独立地是H或-CO 2 R 3; Z选自CH 2 OH，CHO，CN，1H-四唑基，其中X是氧或硫，R7是H，烷基，烯基，环烷基，任选取代的苯基，任选取代的苄基或药学上 可接受的阳离子 并且R 8和R 9独立地为H，烷基或环烷基，或者R 8和R 9一起为 - （CH 2）4 - ， - （CH 2）5 - 或 - （CH 2）2 O（CH 2）2 - 条件是如果X和A是氧，则R1和R7不能都是H。

    Mycophenolic acid derivatives in the treatment of rheumatoid arthritis
    2.
    发明授权
    Mycophenolic acid derivatives in the treatment of rheumatoid arthritis 失效
    霉酚酸衍生物治疗类风湿关节炎

    公开(公告)号：US4725622A

    公开(公告)日：1988-02-16

    申请号：US821633

    申请日：1986-01-23

    申请人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui ,  Joseph M. Muchowski

    发明人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui ,  Joseph M. Muchowski

    IPC分类号： C07D307/88 ,  A61K31/44

    CPC分类号： C07D307/88

    摘要： A method of treating rheumatoid arthritis which method comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein:A is oxygen or sulfur;R.sup.1 is selected from the group consisting of H, ##STR2## in which Y is oxygen or sulfur:R.sup.2 is alkyl, haloalkyl or --NR.sup.4 R.sup.5, where R.sup.4 and R.sup.5 are independently H, alkyl, haloalkyl, cycloalkyl, phenyl optionally monosubstituted with halogen, hydroxy, carboxy, chlorocarbonyl, sulfonylamino, nitro, cyano, phenyl, alkyl, acyl, alkoxycarbonyl, acylamino, dialkylamino or dialkylaminoethoxycarbonyl, phenyl optionally disubstituted with hydroxy, carboxy, nitro or alkyl, or benzyl optionally substituted with dialkylamino;n is an integer from 0-6;R.sup.3 is H alkyl or a pharmaceutically acceptable cation;Q and R are independently H or --CO.sub.2 R.sup.3 ; andZ is selected from the group consisting of ##STR3## in which X is oxygen or sulfur,R.sup.7 is H, alkyl, alkenyl, cycloalkyl, optionally substituted phenyl, optionally substituted benzyl or a pharmaceutically acceptable cation; andR.sup.8 and R.sup.9 are independently H, alkyl or cycloalkyl, or R.sup.8 and R.sup.9 taken together are --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 -- or --(CH.sub.2).sub.2 O(CH.sub.2).sub.2 --;with the proviso that R.sup.1 and R.sup.7 cannot both be H if X and A are oxygen.

    摘要翻译： 治疗类风湿性关节炎的方法，该方法包括向需要这种治疗的哺乳动物施用治疗有效量的下式化合物及其药学上可接受的盐，其中：A为氧或硫; 其中Y是氧或硫：R 2是烷基，卤代烷基或-NR 4 R 5，其中R 4和R 5独立地是H，烷基，卤代烷基，环烷基，任选被卤素单取代的苯基， 羟基，羧基，氯代羰基，磺酰基氨基，硝基，氰基，苯基，烷基，酰基，烷氧基羰基，酰氨基，二烷基氨基或二烷基氨基乙氧基羰基，任选被羟基，羧基，硝基或烷基二取代的苯基或任选被二烷基氨基取代的苄基; n是0-6的整数; R3是H烷基或药学上可接受的阳离子; Q和R独立地是H或-CO 2 R 3; Z选自CH 2 OH，CHO，CN，1H-四唑基，其中X是氧或硫，R 7是H，烷基，烯基，环烷基，任选取代的苯基，任选取代的苄基或药学上 可接受的阳离子 并且R 8和R 9独立地为H，烷基或环烷基，或者R 8和R 9一起为 - （CH 2）4 - ， - （CH 2）5 - 或 - （CH 2）2 O（CH 2）2 - 条件是如果X和A是氧，则R1和R7不能都是H。

    Treatment of autoimmune diseases with mycophenolic acid, and derivatives and formulations thereof
    3.
    发明授权
    Treatment of autoimmune diseases with mycophenolic acid, and derivatives and formulations thereof 失效
    用霉酚酸治疗自身免疫疾病及其衍生物和制剂

    公开(公告)号：US4992467A

    公开(公告)日：1991-02-12

    申请号：US500439

    申请日：1990-03-28

    申请人： Anthony C. Allison ,  Elsie M. Eugui ,  Peter H. Nelson ,  Chee-Liang L. Gu ,  William A. Lee

    发明人： Anthony C. Allison ,  Elsie M. Eugui ,  Peter H. Nelson ,  Chee-Liang L. Gu ,  William A. Lee

    IPC分类号： C07D307/88

    CPC分类号： C07D307/88

    摘要： The compounds and pharmaceutical compositions of Formula A, wherein Z is hydrogen or --C(O)R, Y is hydrogen or morpholinoethyl, and where R is lower alkyl or aryl, and the pharmaceutically acceptable salts thereof, are useful as immunosuppressive agents, particularly for treatment of allograft rejection, especially including cardiac allograft rejection, pancreatic allograft rejection and renal allograft rejection, and for treating autoimmune diabetes. ##STR1##

    摘要翻译： 式A的化合物和药物组合物，其中Z是氢或-C（O）R，Y是氢或吗啉代乙基，其中R是低级烷基或芳基及其药学上可接受的盐可用作免疫抑制剂，特别是 用于治疗同种异体移植排斥反应，特别是包括心脏同种异体移植物排斥反应，胰同种异体移植物排斥反应和肾同种异体移植排斥反应，以及用于治疗自身免疫性糖尿病。 （方程式A）

    Treatment of allograft rejection with mycophenolic acid, its morpholinoethylester and derivatives thereof
    4.
    发明授权
    Treatment of allograft rejection with mycophenolic acid, its morpholinoethylester and derivatives thereof 失效
    用霉酚酸，其吗啉代乙酯及其衍生物治疗同种异体移植排斥

    公开(公告)号：US4868153A

    公开(公告)日：1989-09-19

    申请号：US233200

    申请日：1988-08-17

    申请人： Anthony C. Allison ,  Elsie M. Eugui ,  Peter H. Nelson ,  Chee-Liang L. Gu ,  William A. Lee

    发明人： Anthony C. Allison ,  Elsie M. Eugui ,  Peter H. Nelson ,  Chee-Liang L. Gu ,  William A. Lee

    IPC分类号： C07D307/88

    CPC分类号： C07D307/88

    摘要： The compounds and pharmaceutical compositions of Formula A, wherein Z is hydrogen or --C(O)R, Y is hydrogen or morpholinoethyl, and where R is lower alkyl or aryl, and the pharmaceutically acceptable salts thereof, are useful as immunosuppressive agents, particularly for treatment of allograft rejection, especially including cardiac allograft rejection, pancreatic allograft rejection and renal allograft rejection, and for treating autoimmune diabetes. ##STR1##

    摘要翻译： 式A的化合物和药物组合物，其中Z是氢或-C（O）R，Y是氢或吗啉代乙基，其中R是低级烷基或芳基及其药学上可接受的盐可用作免疫抑制剂，特别是 用于治疗同种异体移植排斥反应，特别是包括心脏同种异体移植物排斥反应，胰同种异体移植物排斥反应和肾同种异体移植排斥反应，以及用于治疗自身免疫性糖尿病。 （方程式A）

    Mycophenolic acid derivatives in the treatment of inflammatory diseases, in particular rheumatoid arthritis
    5.
    发明授权
    Mycophenolic acid derivatives in the treatment of inflammatory diseases, in particular rheumatoid arthritis 失效
    霉酚酸衍生物治疗炎性疾病，特别是类风湿性关节炎

    公开(公告)号：US4686234A

    公开(公告)日：1987-08-11

    申请号：US803041

    申请日：1985-11-27

    申请人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui

    发明人： Peter H. Nelson ,  Anthony C. Allison ,  Elsie M. Eugui

    IPC分类号： C07D407/12 ,  C07D307/88

    CPC分类号： C07D407/12

    摘要： Compounds useful for treating inflammatory diseases, in particular rheumatoid arthritis, represented by the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein:R.sub.1 is H or lower alkyl having 1 to 6 carbon atoms;R.sub.2 is H, lower alkyl having 1 to 6 carbon atoms or ##STR2## in which R.sub.3 is H, lower alkyl having 1 to 6 carbon atoms or a pharmaceutically acceptable cation;R.sub.4 and R.sub.5 are each independently H or lower alkyl having 1 to 6 carbon atoms;X and Y are each independently O or S; andn is an integer of 1-6.

    摘要翻译： 用于治疗由下式表示的炎性疾病，特别是类风湿性关节炎的化合物及其药学上可接受的盐，其中：R 1是H或具有1至6个碳原子的低级烷基; R2是H，具有1至6个碳原子的低级烷基或其中R 3是H的低级烷基或具有1至6个碳原子的低级烷基或其药学上可接受的阳离子; R4和R5各自独立地为具有1至6个碳原子的H或低级烷基; X和Y各自独立地为O或S; n为1-6的整数。