GlaxoSmithKline Medicines Research Centre, Neurosciences Centre of Excellence for Drug Discovery, Via Fleming 4, 37135 Verona, Italy.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6899-904. doi: 10.1016/j.bmcl.2011.07.116. Epub 2011 Aug 6.
During the lead optimization of NK(1)/NK(3) receptor antagonists program, a focused exploration of molecules bearing a lactam moiety was performed. The aim of the investigation was to identify the optimal position of the carbonyl and hydroxy methyl group in the lactam moiety, in order to maximize the in vitro affinity and the level of insurmountable antagonism at both NK(1) and NK(3) receptors. The synthesis and biological evaluation of these novel lactam derivatives, with potent and balanced NK(1)/NK(3) activity, were reported in this paper.
在 NK(1)/NK(3)受体拮抗剂项目的先导优化过程中，我们对含有内酰胺部分的分子进行了重点研究。我们的研究目的是确定内酰胺部分中羰基和羟甲基的最佳位置，以最大限度地提高化合物对 NK(1)和 NK(3)受体的体外亲和力和不可逾越拮抗作用的水平。本文报道了这些具有强大且平衡的 NK(1)/NK(3)活性的新型内酰胺衍生物的合成和生物学评价。
