Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 2011 May 15;21(10):2890-3. doi: 10.1016/j.bmcl.2011.03.083. Epub 2011 Mar 30.
A novel series of pyridazinone analogs has been developed as potent β-1,3-glucan synthase inhibitors through structure-activity relationship study of the lead 5-[4-(benzylsulfonyl)piperazin-1-yl]-4-morpholino-2-phenyl-pyridazin-3(2H)-one (1). The effect of changes to the core structure is described in detail. Optimization of the sulfonamide moiety led to the identification of important compounds with much improved systematic exposure while retaining good antifungal activity against the fungal strains Candida glabrata and Candida albicans.
通过对先导化合物 5-[4-(苄基磺酰基)哌嗪-1-基]-4-吗啉基-2-苯基-哒嗪-3(2H)-酮（1）的结构-活性关系研究，开发了一系列新型哒嗪酮类似物作为强效的β-1,3-葡聚糖合成酶抑制剂。本文详细描述了对核心结构进行改变的效果。对磺酰胺部分进行优化，得到了一些重要的化合物，在保留对真菌菌株光滑念珠菌和白色念珠菌良好抗真菌活性的同时，显著提高了系统暴露量。
