Hatzenbuhler Nicole T, Evrard Deborah A, Harrison Boyd L, Huryn Donna, Inghrim Jennifer, Kraml Christina, Mattes James F, Mewshaw Richard E, Zhou Dahui, Hornby Geoffrey, Lin Qian, Smith Deborah L, Sullivan Kelly M, Schechter Lee E, Beyer Chad E, Andree Terrance H
Chemical and Screening Sciences and Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA.
J Med Chem. 2006 Jul 27;49(15):4785-9. doi: 10.1021/jm060218h.
Compounds containing a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran and a 3-alkylindole moiety linked through a common basic nitrogen were prepared and evaluated for 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonist activity in vitro. 26a was found to be the most potent and selective compound in this series and was shown to possess neurochemical activity in vivo by producing acute and rapid increases in 5-HT in the rat frontal cortex.
制备了含有通过一个共同碱性氮连接的5-氨甲酰基-8-氟-3-氨基-3,4-二氢-2H-1-苯并吡喃和3-烷基吲哚部分的化合物，并对其进行了体外5-HT1A亲和力、血清素大鼠转运体亲和力和功能性拮抗剂活性的评估。发现26a是该系列中最有效和最具选择性的化合物，并且通过使大鼠额叶皮质中的5-HT急性快速增加，在体内表现出神经化学活性。
