Piergentili A, Pigini M, Quaglia W, Tayebati S K, Amenta F, Sabbatini M, Giannella M
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Bioorg Med Chem. 1996 Dec;4(12):2193-9. doi: 10.1016/s0968-0896(96)00231-3.
Some thio- and the benzoyl-derivatives of deoxamuscarine were synthesized and tested as muscarinic agonists using radioligand binding assays and functional tests. In comparison with deoxamuscarine, used as reference compound, no dimension/distance modification is tolerated for correct lipophilic pocket recognition. The substitution of the ammonium group with a sulphonium group significantly decreased muscarinic potency. The so-called 'muscarinic sub-site' accepts relatively bulky functions as long as it is bound to the cyclopentane carrier by an oxygen bridge. Esterification of this moiety increases the M2 subtype selectivity, while etherification heightens that of M3.
合成了去氧毒蕈碱的一些硫代和苯甲酰衍生物，并使用放射性配体结合试验和功能测试作为毒蕈碱激动剂进行了测试。与用作参考化合物的去氧毒蕈碱相比，为了正确识别亲脂性口袋，不允许有尺寸/距离的改变。用锍基团取代铵基团会显著降低毒蕈碱活性。只要通过氧桥与环戊烷载体相连，所谓的“毒蕈碱亚位点”就能接受相对较大的官能团。该部分的酯化增加了M2亚型的选择性，而醚化则提高了M3亚型的选择性。
