Picolinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to 5-HT_1A, 5-HT_2A and 5-HT_2C receptors was evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine), known to play critical roles in affinity for serotoninergic receptors, and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed high affinity in nanomolar and subnanomolar range at 5-HT_1A, 5-HT_2A and 5-HT_2C receptors and moderate or no affinity for other relevant receptors (D₁, D₂, α₁ and α₂). N-(2-(4-(pyrimidin-2-yl)piperazin-1-yl)ethyl)picolinamide (3o) with Ki = 0.046 nM, was the most affine and selective derivative for the 5-HT_1A receptor compared to other serotoninergic dopaminergic and adrenergic receptors. N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)picolinamide (3b), instead, showed a subnanomolar affinity towards 5-HT_2A with Ki = 0.0224 nM, whereas N-(2-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)ethyl)picolinamide (3s) presented an attractive 5-HT_2C affinity with K_i = 0.8 nM. Moreover, the compounds having better affinity and selectivity binding profiles towards 5-HT_2A were selected and tested on rat ileum, to determine their effect on 5HT induced contractions. Those more selective towards 5-HT_1A receptors were studied in vivo on several behavioral tests.

制备了连接至芳基哌嗪部分的吡啶甲酸酰胺衍生物，并评估了它们对5-HT _1A，5-HT _2A和5-HT _2C受体的亲和力。结构元件的组合（杂环核，烷基链和4-取代的哌嗪），已知在对血清素受体的亲和力以发挥关键作用，并导致以高特异性和亲和力向血清素受体的化合物的取代基的正确选择。在结合研究中，几个分子在5-HT _1A，5-HT _2A和5-HT _2C受体的纳摩尔和亚纳摩尔范围内显示出高亲和力，而对其他相关受体（D ₁，D ₂，α ₁和α ₂）。Ki = 0.046 nM的N-（2-（4-（嘧啶-2-基）哌嗪-1-基）乙基）吡啶啉酰胺（3o）是5-HT _1A受体的亲和力和选择性最高的衍生物5-羟色胺能的多巴胺能和肾上腺素能受体。N-（2-（4-（2-（2-甲氧基苯基）哌嗪-1-基）乙基）吡啶啉酰胺（3b）显示对5-HT _2A的亚纳摩尔亲和力，Ki = 0.0224 nM，而N-（2-（ 4-（双（4-氟苯基）甲基）哌嗪-1-基）乙基吡啶啉酰胺（3s）表现出有吸引力的5-HT _2C亲和力，K _i  = 0.8 nM。此外，这些化合物对5-HT具有更好的亲和力和选择性结合特征选择_2A并在大鼠回肠上测试，以确定它们对5HT诱导的收缩的作用。在一些行为测试中，对那些对5-HT _1A受体更具选择性的物质进行了体内研究。