Mokrov G V, Deeva O A, Gudasheva T A, Yarkov S A, Yarkova M A, Seredenin S B
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
Federal State Budgetary Institution 'Research Zakusov Institute of Pharmacology', Baltiyskaya Str., 8, Moscow 125315, Russia.
Bioorg Med Chem. 2015 Jul 1;23(13):3368-78. doi: 10.1016/j.bmc.2015.04.049. Epub 2015 Apr 23.
A series of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides were designed and synthesized as 18kDa translocator protein (TSPO) ligands. Anxiolytic-like activity of compounds was evaluated in the open field test and elevated plus maze test. Compounds 1a and 1b demonstrated high anxiolytic-like effect in the dose range of 0.1-1.0mg/kg comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by antagonism of the most active compound 1a with TSPO selective inhibitor PK11195. In vitro binding studies demonstrated high TSPO affinities for compounds 1a and 1b.
设计并合成了一系列1-芳基吡咯并[1,2-a]吡嗪-3-甲酰胺作为18kDa转位蛋白（TSPO）配体。在旷场试验和高架十字迷宫试验中评估了化合物的抗焦虑样活性。化合物1a和1b在0.1-1.0mg/kg剂量范围内表现出与地西泮相当的高抗焦虑样作用。最具活性的化合物1a与TSPO选择性抑制剂PK11195的拮抗作用证明了TSPO受体参与了新化合物抗焦虑样活性的机制。体外结合研究表明化合物1a和1b对TSPO具有高亲和力。
