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    • 2. 发明授权
    • Optically active isocarbostyril derivatives and a method of preparing
the same
    • 光活性异卡波斯特尔衍生物及其制备方法
    • US4659833A
    • 1987-04-21
    • US731963
    • 1985-05-08
    • Toshihiro TakahashiNoriyoshi SuedaMasahiro TsujiYoshiyuki TaharaHiroyasu KoyamaYoshikuni SuzukiMasao NagaseToshiji Sugai
    • Toshihiro TakahashiNoriyoshi SuedaMasahiro TsujiYoshiyuki TaharaHiroyasu KoyamaYoshikuni SuzukiMasao NagaseToshiji Sugai
    • C07D215/56A61K31/47A61K31/472A61P9/00A61P9/08A61P9/10A61P9/12A61P25/02C07D209/48C07D209/49C07D217/24C07D405/12C07D413/12
    • C07D413/12C07D217/24
    • Four different optical isomers of a new compound, 1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanol are now provided as new substances. These four optical isomers are now named as (2R, 1'S)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanol, (2S, 1'S)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanol, (2S, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanol, and (2R, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanol, respectively. These four optical isomers have different activities for their .beta.-adrenergic-blocking effect and .alpha.-adrenergic-blocking effect and are useful as valuable agents for therapeutic treatment of various cardiovascular diseases, as compared to an optically inactive racemic mixture of said isomer compounds. These four optical isomers may be produced and isolated from each other by chromatographing (1'S)- or (1'R)-N-[2'-(o-methoxyphenoxy)-1'-methylethyl]-5-(4"-isocarbostyriloxymethyl)-2-oxazolidones to isolate either its (5R, 1'S)-isomer and its (5S, 1'S)-isomer, or its (5S, 1'R)-isomer and its (5R, 1'R)-isomer therefrom separately and then hydrolyzing each of these isolated isomers under alkaline conditions to obtain separately (2R, 1'S)-, (2S, 1'S)-, (2S, 1'R)- and (2R, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4"-isocarbostyriloxy)-2-propanols.
    • 现在提供新的化合物1- [2' - (邻甲氧基苯氧基)-1'-甲基乙基氨基] -3-(4“ - 异卡波酰氧基)-2-丙醇的四种不同的光学异构体作为新物质。 这些四种光学异构体现在命名为(2R,1'S)-1- [2' - (邻甲氧基苯氧基)-1'-甲基乙基氨基] -3-(4“ - 异卡波铵氧基)-2-丙醇,(2S, 1'S)-1- [2' - (邻甲氧基苯氧基)-1'-甲基乙基氨基] -3-(4“ - 异卡波铵氧基)-2-丙醇,(2S,1'R)-1- [ (邻甲氧基苯氧基)-1'-甲基乙基氨基] -3-(4“ - 异卡波铵氧基)-2-丙醇和(2R,1'R)-1- [2' - (邻甲氧基苯氧基) - 甲基乙基氨基] -3-(4“ - 异卡波铵氧基)-2-丙醇。 与所述异构体化合物的光学上无活性的外消旋混合物相比,这四种光学异构体对于β-肾上腺素能阻滞效应和α-肾上腺素能阻断效应具有不同的活性,并且可用作治疗各种心血管疾病的有价值的药剂。 这些四种光学异构体可以通过色谱法(1'S) - 或(1'R)-N- [2' - (邻甲氧基苯氧基)-1'-甲基乙基] -5-(4“ - (5R,1'S) - 异构体或其(5S,1'R) - 异构体及其(5R,1'R) - 异构体 然后分别在碱性条件下水解这些分离的异构体,分别得到(2R,1'S) - ,(2S,1'S) - ,(2S,1'R) - 和(2R,1'R)-1- [ 2' - (邻甲氧基苯氧基)-1'-甲基乙基氨基] -3-(4“ - 异卡波铵氧基)-2-丙醇。