Barlocco D, Fanelli F, Cignarella G, Villa S, Cattabeni F, Balduini W, Cimino M, De Benedetti P G
Drug Des Discov. 1996 Oct;14(2):129-43.
A series of 2-(acyl)amino-8-substituted-2,8-diazaspiro[4,5]decan-1,3-diones (5a-j), structurally related to the muscarinic agonist RS-86, was synthesized and compounds tested for their affinity towards muscarinic receptors. Though all compounds proved to be less active than the model in binding studies, only three derivatives (5a, b, c) being able to significantly displace 3H-QNB at mM concentration, their behaviour could be interpreted in terms of theoretical molecular descriptors computed on the basis of the suggestions coming from Molecular Dynamics simulations of ligand-receptor complexes.
合成了一系列与毒蕈碱激动剂RS-86结构相关的2-(酰基)氨基-8-取代-2,8-二氮杂螺[4,5]癸烷-1,3-二酮(5a-j)，并测试了这些化合物对毒蕈碱受体的亲和力。尽管在结合研究中所有化合物的活性均低于模型化合物，只有三种衍生物(5a、b、c)在毫摩尔浓度下能够显著取代3H-QNB，但根据基于配体-受体复合物分子动力学模拟得出的建议计算的理论分子描述符，可以解释它们的行为。
