The approach of tethering together two known receptor ligands, to be used as molecular probes for the study of G protein-coupled receptor (GPCR) systems, has proven to be a valuable approach. Selective ligands that possess functionality that can be used to link to other ligands, are useful in the development of novel antagonists and agonists. Such molecules can also be attached to reporter molecules, such as fluorophores, for the study of GPCR dimerization and its role in signaling. The highly selective serotonin (5-HT) 5-HT_2A receptor (5-HT_2AR) antagonist M100907 (volinanserin) is of clinical interest in the treatment of neurological and mental health disorders. Here, we synthesized the most active (+)-M100907 enantiomer as well as a series of derivatives that possessed either an alkyne or an azide. The triazole resulting from the dipolar cycloaddition of these groups did not interfere with the ability of the bivalent ligand to act as an antagonist. Thus, we have synthesized a number of compounds which will prove useful in elucidating the role of the 5-HT_2AR in the central nervous system.

将两个已知的受体配体连接在一起的方法被用作有价值的方法，该方法用作研究G蛋白偶联受体（GPCR）系统的分子探针。具有可用于与其他配体连接的功能的选择性配体可用于开发新型拮抗剂和激动剂。此类分子还可以连接到报告分子（例如荧光团）上，以研究GPCR二聚化及其在信号传导中的作用。高选择性5-羟色胺（5-HT）5-HT _2A受体（5-HT _2AR）拮抗剂M100907（volinanserin）在治疗神经和精神疾病方面具有临床意义。在这里，我们合成了活性最高的（+）-M100907对映异构体以及一系列具有炔烃或叠氮化物的衍生物。由这些基团的偶极环加成产生的三唑不干扰二价配体充当拮抗剂的能力。因此，我们合成了许多化合物，这些化合物将被证明可用于阐明5-HT _2A R在中枢神经系统中的作用。