Wyatt P G, Coomber B A, Evans D N, Jack T I, Fulton H E, Wonacott A J, Colman P, Varghese J
Department of Medicinal Chemistry, Glaxo Wellcome Medicines Research Centre, Stevenage, Herts, UK.
Bioorg Med Chem Lett. 2001 Mar 12;11(5):669-73. doi: 10.1016/s0960-894x(01)00019-1.
SAR investigations of the 4- and 5-positions of a series of 4-amino-4H-pyran-2-carboxylic acid 6-carboxamides are reported. Potent inhibitors of influenza A sialidase with marked selectivity over the influenza B enzyme were obtained when the basic 4-amino substituent was replaced by hydroxyl or even deleted. Modifications at the 5-position exhibited a tight steric requirement, with trifluoroacetamide being optimal.
报道了一系列4-氨基-4H-吡喃-2-羧酸6-羧酰胺4位和5位的构效关系研究。当碱性的4-氨基取代基被羟基取代甚至去除时，可得到对甲型流感病毒唾液酸酶有强效抑制作用且对乙型流感病毒酶具有显著选择性的抑制剂。5位的修饰显示出严格的空间要求，三氟乙酰胺为最佳。
