Olberg Dag Erlend, Andressen Kjetil Wessel, Levy Finn Olav, Klaveness Jo, Haraldsen Ira, Sutcliffe Julie L
Norwegian Medical Cyclotron Centre, PO Box 4950, Nydalen, N-0424 Oslo, Norway.
Department of Pharmacology, Faculty of Medicine, University of Oslo, Norway.
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1846-50. doi: 10.1016/j.bmcl.2014.02.002. Epub 2014 Feb 10.
Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. LogP (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. (18)F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.
合成了两种新型的呋酰胺类小分子促性腺激素释放激素（GnRH）受体拮抗剂（12和13），并在体外评估了它们对大鼠GnRH受体的受体结合亲和力。研究了在一步反应中用无载体添加的氟-18对合适前体进行放射性标记。研究了化合物的LogP（辛醇/磷酸盐缓冲液pH 7.4）和血清稳定性。这些拮抗剂对大鼠GnRH受体显示出低纳摩尔亲和力。以高放射化学纯度（>95%）和比活度（>75 GBq/μmol）获得了（18）F放射性标记的化合物。这些发现表明这类化合物有望作为正电子发射断层扫描（PET）靶向GnRH受体表达的潜在探针。
