恽榴红, 文广伶, 张其楷. 解胆碱能药物:二苯乙基氮杂环烃衍生物的合成J. 药学学报, 1984, 19(9): 671-675.
引用本文: 恽榴红, 文广伶, 张其楷. 解胆碱能药物:二苯乙基氮杂环烃衍生物的合成J. 药学学报, 1984, 19(9): 671-675.
YUN Liu-Hong, WEN Guang-Iing , ZHANG Qi-Kai, . ANTICHOLINERGICS:SYNTHESIS OF 2',2'-DIPHENYLETHYL AZACYCLOALKANE DERIVATIVESJ. Acta Pharmaceutica Sinica, 1984, 19(9): 671-675.
Citation: YUN Liu-Hong, WEN Guang-Iing , ZHANG Qi-Kai, . ANTICHOLINERGICS:SYNTHESIS OF 2',2'-DIPHENYLETHYL AZACYCLOALKANE DERIVATIVESJ. Acta Pharmaceutica Sinica, 1984, 19(9): 671-675.

解胆碱能药物:二苯乙基氮杂环烃衍生物的合成

ANTICHOLINERGICS:SYNTHESIS OF 2',2'-DIPHENYLETHYL AZACYCLOALKANE DERIVATIVES

  • 摘要: 3-(2′,2′-二苯乙基)托品烷(L)具有较强的抗M胆碱能作用和中枢抗震颤作用。为了了解托品环在结构(L)中的重要性,以期获得更好的药物,以4种不同氮杂环烃分别取代(L)及其衍生物中的托品环,合成了12个类似化合物。动物实验结果表明由3-喹宁环基、N-甲基-4-哌啶基、N-苄基-4-哌啶基、N-甲基-3-氮杂双环-(3,3,1)壬-9-烷基分别取代结构(L)的托品环,均导致中枢和周围解胆碱能作用下降。

     

    Abstract: 3-Quinuclidinyl, N-methylpiperidin-4-yl, N-benzylpiperidin-4-yl, N-methyl-3-azabicyclo (3,3,1)nonan-9-yl, which were found in molecular structures of some stronger anticholinergics, were selected to displace tropanyl in 3-(2′, 2′-diphenylethyl) tropane (L) and its derivatives Twelve compounds (Ⅳ1~4,Ⅴ1~4, Ⅵ1~4) were synthesized. With Raney Ni in ethanol, compounds Ⅴ1 and Ⅴ4 could be catalytically hydrogenated smoothly to compounds Ⅵ1 and Ⅵ4, but compounds Ⅴ2 and Ⅴ3 could not in the same condition. And with 10% Pd/C in glacial acetic acid, Ⅴ2 and Ⅴ3 could be hydrogenated to Ⅵ2 and Ⅵ3. Animal tests (mydriasis, antisalivary secretion and antiarecoline tremor) showed that the anticholinergic activities of these compounds were weaker than those of the lead compound (L) and atropine.

     

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