解胆碱能药物:二苯乙基氮杂环烃衍生物的合成

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。

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

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 (Ⅳ_1～4,Ⅴ_1～4, Ⅵ_1～4) 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.