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    Pyrimidine type mevalonolactones
    4.
    发明授权
    Pyrimidine type mevalonolactones 失效
    嘧啶型甲羟戊酸内酯

    公开(公告)号：US5026708A

    公开(公告)日：1991-06-25

    申请号：US243468

    申请日：1988-09-12

    申请人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    发明人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    IPC分类号： C07D239/26 ,  C07D405/06

    CPC分类号： C07D239/26 ,  C07D405/06

    摘要： A compound of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.1-3 alkoxy, n-butoxy, i-butoxy, sec-butoxy, R.sup.5 R.sup.6 N-- (wherein R.sup.5 and R.sup.6 are independently hydrogen or C.sub.1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.15 (wherein R.sup.15 is hydrogen or C.sub.1-3 alkyl, and l is 1, 2 or 3); or when located at the ortho position to each other, R.sup.1 and R.sup.2 together form --CH.dbd.CH--CH.dbd.CH-- or methylene dioxy; Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH-- or --CH.dbd.CH--CH.sub.2 --; Z is --Q--CH.sub.2 WCH.sub.2 --CO.sub.2 R.sup.12, ##STR2## (wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--; W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11) (OH)--; R.sup.11 is hydrogen or C.sub.1-3 alkyl; R.sup.12 is hydrogen or R.sup.14 (wherein R.sup.14 is physiologically hydrolyzable alkyl or M (wherein M is NH.sub.4, sodium, potassium, 1/2 calcium or a hydrate of lower alkylamine, di-lower alkylamine or tri-lower alkylamine)); two R.sup.13 are independently primary or secondary C.sub.1-6 alkyl; or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 --; R.sup.16 and R.sup.17 are independently hydrogen or C.sub.1-3 alkyl; R.sup.3 is hydrogen, C.sub.1-6 alkyl, C.sub.2-3 alkenyl, C.sub.3-6 cycloalkyl, ##STR3## (wherein R.sup.7 is hydrogen, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, fluoro, chloro, bromo or trifluoromethyl), phenyl--(CH.sub.2).sub.m -- (wherein m is 1, 2 or 3), --(CH.sub.2).sub.n CH(CH.sub.3)--phenyl or phenyl--(CH.sub.2).sub.n CH(CH.sub.3)-- (wherein n is 0, 1 or 2): R.sup.4 is C.sub.1-8 alkyl, C.sub.3-7 cycloalkyl, .alpha.- or .beta.-naphthyl, 2--, 3-- or 4-pyridyl, ##STR4## (wherein R.sup.8, R.sup.9 and R.sup.10 are independently hydrogen, C.sub.1-4 alkyl, C.sub.1-8 alkoxy, C.sub.1-3 alkylthio, chloro, bromo, fluoro, --NR.sup.18 R.sup.19 (wherein R.sup.18 and R.sup.19 are independently C.sub.1-3 alkyl), trichloromethyl, trifluoromethyl, trifluoromethoxy, difluoromethoxy, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.k OR.sup.20 (wherein R.sup.20 is hydrogen or C.sub.1-3 alkyl, and k is 1, 2 or 3); when R.sup.10 is hydrogen and when located at the ortho position to each other, R.sup.8 and R.sup.9 together form --OC(R.sup.23) (R.sup.24)O-- (wherein R.sup.23 and R.sup.24 are independently hydrogen or C.sub.1-3 alkyl)), ##STR5## (wherein R.sup.25 is hydrogen, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, chloro, bromo, or fluoro) or C.sub.1-3 alkyl substituted by 1 member selected from the group consisting of ##STR6## (wherein R.sup.8, R.sup.9 and R.sup.10 are as defined above) and naphthyl and by 0, 1 or 2 members selected from the group consisting of C.sub.1-8 alkyl.

    Quinoline type mevalonolactones useful for treating hyperlipidemia and related diseases
    6.
    发明授权
    Quinoline type mevalonolactones useful for treating hyperlipidemia and related diseases 失效
    适用于治疗高脂血症和相关疾病的喹诺酮类型的美洛酮

    公开(公告)号：US5102888A

    公开(公告)日：1992-04-07

    申请号：US483724

    申请日：1990-02-23

    申请人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    发明人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    IPC分类号： A61K31/47 ,  A61K31/473 ,  A61P3/06 ,  A61P7/00 ,  A61P9/10 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D215/20 ,  C07D215/38 ,  C07D215/54 ,  C07D221/06 ,  C07D405/06 ,  C07D491/056

    CPC分类号： C07D405/06 ,  C07D215/14 ,  C07D215/18 ,  C07D215/20

    摘要： A compound of the formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are independently hydrogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, C.sub.1-3 alkoxy, n-botoxy, i-botoxy, sec-butoxy, R.sup.7 R.sup.8 N-- (wherein R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.19 (wherein R.sup.19 is hydrogen or C.sub.1-3 alkyl, and l is 1,2 or 3); or when located at the ortho position to each other, R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together form --CH.dbd.CH--CH.dbd.CH--; or when located at the ortho position to each other, R.sup.1 and R.sup.2 together form --OC(R.sup.15) (R.sup.16)O--(wherein R.sup.15 and R.sup.16 are independently hydrogen or C.sub.1-3 alkyl); Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH-- or -- CH.dbd.CH--CH.sub.2 --; and Z is --Q--CH.sub.2 WCH.sub.2 --CO.sub.2 R.sup.12, ##STR2## (wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--; W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11) (OH)--; R.sup.11 is hydrogen atom or C.sub.1-3 alkyl; R.sup.12 is hydrogen or R.sup.14 (wherein R.sup.14 is physiologically hydrolyzable alkyl or M (wherein M is NH.sub.4, sodium, potassium, 1/2 calcium or a hydrate of lower alkyl amine, di-lower alkyl amine or tri-lower alkyl amine)); two R.sup.13 are independently primary or secondary C.sub.1-6 alkyl; or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 ; R.sup.17 and R.sup.18 are independently hydrogen or C.sub.1-3 alkyl; and R.sup.5 is hydrogen, C.sub.1-6 alkyl, C.sub.2-3 alkenyl, C.sub.3-6 cycloalkyl, ##STR3## wherein R.sup.9 is a hydrogen atom, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, fluoro, chloro, bromo or trifluoromethyl), phenyl-(CH.sub.2).sub.m -- (wherein m is 1,2 or 3), --(CH.sub.2).sub.n CH(CH.sub.3)--phenyl or phenyl--(CH.sub.2).sub.n CH(CH.sub.3)-- (wherein n is 0,1 or 2).

    Quinoline type mevalonolactones
    7.
    发明授权
    Quinoline type mevalonolactones 失效
    喹啉型甲羟戊酸内酯

    公开(公告)号：US5011930A

    公开(公告)日：1991-04-30

    申请号：US483720

    申请日：1990-02-23

    申请人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    发明人： Yoshihiro Fujikawa ,  Mikio Suzuki ,  Hiroshi Iwasaki ,  Mitsuaki Sakashita ,  Masaki Kitahara

    IPC分类号： A61K31/47 ,  A61K31/473 ,  A61P3/06 ,  A61P7/00 ,  A61P9/10 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D215/20 ,  C07D215/38 ,  C07D215/54 ,  C07D221/06 ,  C07D405/06 ,  C07D491/056

    CPC分类号： C07D405/06 ,  C07D215/14 ,  C07D215/18 ,  C07D215/20

    摘要： A compound of the formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are independently hydrogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, C.sub.1-3 alkoxy, n-botoxy, i-botoxy, sec-butoxy, R.sup.7 R.sup.8 N-- (wherein R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.19 (wherein R.sup.19 is hydrogen or C.sub.1-3 alkyl, and l is 1,2 or 3); or when located at the ortho position to each other, R.sup.1 and R.sup.2, and R.sup.3 and R.sup.4 together form --CH.dbd.CH--CH.dbd.CH--; or when located at the ortho position to each other, R.sup.1 and R.sup.2 together form --OC(R.sup.15)(R.sup.16)O-- (wherein R.sup.15 and R.sup.16 are independently hydrogen or C.sub.1-3 alkyl); Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 CH.dbd.CH-- or --CH.dbd.CH-- CH.sub.2 --; and Z is --Q--CH.sub.2 WCH.sub.2 --CO.sub.2 R.sup.12, ##STR2## (wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--; W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11)(OH)--; R.sup.11 is hydrogen atom or C.sub.1-3 alkyl; R.sup.12 is hydrogen or R.sup.14 (wherein R.sup.14 is physiologically hydrolyzable alkyl or M (wherein M is NH.sub.4, sodium, potassium, 1/2 calcium or a hydrate of lower alkyl amine, di-lower alkyl amine or tri-lower alkyl amine)); two R.sup.13 are independently primary or secondary C.sub.1-6 alkyl; or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 ; R.sup.17 and R.sup.18 are independently hydrogen or C.sub.1-3 alkyl; and R.sup.5 is hydrogen, C.sub.1-6 alkyl, C.sub.2-3 alkenyl, C.sub.3-6 cycloalkyl, ##STR3## (wherein R.sup.9 is a hydrogen atom, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, fluoro, chloro, bromo or trifluoromethyl), phenyl-(CH.sub.2).sub.m -- (wherein m is 1,2 or 3), --(CH.sub.2).sub.n CH(CH.sub.3)-phenyl or phenyl-(CH.sub.2).sub.n CH(CH.sub.3)-- (wherein n is 0,1 or 2).

    摘要翻译： 下式的化合物：其中R 1，R 2，R 3，R 4和R 6独立地是氢，C 1-6烷基，C 1-6环烷基，C 1-3烷氧基，正丁氧基，异丁氧基，仲丁氧基， 丁氧基，R7R8N-（其中R7和R8独立地是氢或C1-3烷基），三氟甲基，三氟甲氧基，二氟甲氧基，氟，氯，溴，苯基，苯氧基，苄氧基，羟基，三甲基甲硅烷氧基，二苯基叔丁基甲硅烷氧基，羟甲基或 - O（CH 2）lOR 19（其中R 19是氢或C 1-3烷基，且l是1,2或3）; 或当位于彼此的邻位时，R1和R2以及R3和R4一起形成-CH = CH-CH = CH-; 或者当位于彼此的邻位时，R 1和R 2一起形成-OC（R 15）（R 16）O-（其中R 15和R 16独立地是氢或C 1-3烷基）; Y是-CH 2 - ， - CH 2 CH 2 - ， - CH = CH - ， - CH 2 CH = CH-或-CH = CH-CH 2 - ; （其中Q为-C（O） - ， - C（OR 13）2 - 或-CH（OH） - ）; W为-C（O） - （CH 2） ，-C（OR 13）2 - 或-C（R 11）（OH） - ; R 11为氢原子或C 1-3烷基; R 12为氢或R 14（其中R 14为生理上可水解的烷基或M（其中M为NH 4，钠 ，二价低级烷基胺或三低级烷基胺的水合物））;两个R 13独立地为伯或仲C 1-6烷基;或两个R 13一起形成 - （CH 2） 2-或 - （CH 2）3; R 17和R 18独立地是氢或C 1-3烷基;且R 5是氢，C 1-6烷基，C 2-3烯基，C 3-6环烷基，其中R 9是氢 苯基 - （CH 2）m - （其中m为1,2或3）， - （CH 2）n CH（CH 3） - 苯基或（C 1 -C 4）烷基，C 1-4烷氧基，氟，氯，溴或三氟甲基） 苯基 - （CH 2）n CH（CH 3） - （其中n为0,1或2）。