Hamprecht Dieter, Micheli Fabrizio, Tedesco Giovanna, Donati Daniele, Petrone Marcella, Terreni Silvia, Wood Martyn
GlaxoSmithKline, Medicine Research Centre, Via Fleming, 4, 37135 Verona, Italy.
Bioorg Med Chem Lett. 2007 Jan 15;17(2):424-7. doi: 10.1016/j.bmcl.2006.10.034. Epub 2006 Oct 17.
Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level.
报道了一系列新型三环选择性5-HT2C受体拮抗剂的设计、合成及性质。对2-苯基-二氢吡咯酮骨架的构象分析表明，环融合可使该部分环之间的共平面性固定，而5-HT2C受体可能对此有所耐受。这样做的一个有趣效果是内酰胺环中碳-碳双键的性质从乙烯基变为芳基。研究发现这些变化在受体水平和体内水平均产生了良好的特性。
