Rodriguez Fernando, Rozas Isabel, Ortega Jorge E, Erdozain Amaia M, Meana J Javier, Callado Luis F
Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
J Med Chem. 2009 Feb 12;52(3):601-9. doi: 10.1021/jm800838r.
In this paper, we report the synthesis of three new 2-aminoimidazoline (compounds 4b, 5b, and 6b) and three new guanidine derivatives (compounds 7b, 8b, and 9b) as potential alpha(2)-adrenoceptor antagonists for the treatment of depression. Their pharmacological profile was evaluated in vitro in human brain tissue and compared to the potential antidepressant 1 and the agonists 2 and 3. All new substrates were evaluated by in vitro functional [(35)S]GTPgammaS binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Compound 8b was found to be an antagonist in vitro and was subjected to in vivo microdialysis experiments in rats. Moreover, a new synthesis of the precursor amines for compounds 4b-9b is presented.
在本文中，我们报道了三种新型2-氨基咪唑啉（化合物4b、5b和6b）以及三种新型胍衍生物（化合物7b、8b和9b）的合成，这些化合物作为潜在的α(2)-肾上腺素能受体拮抗剂用于治疗抑郁症。在人脑组织中对它们的药理学特性进行了体外评估，并与潜在的抗抑郁药1以及激动剂2和3进行了比较。通过体外功能性[(35)S]GTPγS结合试验在人前额叶皮质中对所有新底物进行评估，以确定它们的激动或拮抗活性。发现化合物8b在体外是一种拮抗剂，并在大鼠体内进行了微透析实验。此外，还介绍了化合物4b - 9b前体胺的一种新合成方法。
