Audia V H, McPherson D W, Weitzberg M, Rzeszotarski W J, Sturm B, Kachur J F, Abreu M, Kaiser C
Nova Pharmaceutical Corporation, Baltimore, Maryland 21224-2788.
J Med Chem. 1990 Jan;33(1):307-10. doi: 10.1021/jm00163a050.
A series of 3-quinuclidinyl atrolactate [3-(1-azabicyclo[2.2.2]octyl) 2-hydroxy-2-phenylpropionate, QNA] derivatives in which the methyl group of the parent is substituted with a tertiary amino substituent was prepared and tested for antimuscarinic activity. In general, potency was markedly decreased, although the morpholinyl and thiomorpholinyl derivatives retained significant activity. These compounds were also examined for muscarinic receptor subtype selectivity. Their subtype selectivities were comparable to that of (R,R)-QNA. The results of this investigation suggest possible differences in the accessory binding sites of the proteinaceous receptor subtypes.
制备了一系列3-奎宁环基阿托乳酸酯[3-(1-氮杂双环[2.2.2]辛基)2-羟基-2-苯基丙酸酯，QNA]衍生物，其中母体的甲基被叔氨基取代基取代，并测试了它们的抗毒蕈碱活性。一般来说，活性显著降低，尽管吗啉基和硫代吗啉基衍生物仍保留显著活性。还研究了这些化合物对毒蕈碱受体亚型的选择性。它们的亚型选择性与(R,R)-QNA相当。这项研究结果表明蛋白质受体亚型的辅助结合位点可能存在差异。
