[1,2,4]Triazole derivatives as 5-HT_1A serotonin receptor ligands

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• 作者：Sarvà ; Maria Concetta ; Romeo ; Giuseppe ; Guerrera ; Francesco ; Siracusa ; Mariangela ; et. al.
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2002
• 出版时间：February, 2002
• 年：2002
• 卷：10
• 期：2
• 页码：313-323
• 全文大小：192 K

文摘

A series of new 4-amino-3-[3-[4-(2-methoxy or nitro phenyl)-1-piperazinyl] propyl]thio]-5-(substitutedphenyl)[1,2,4]triazoles 11a–t was synthesized in order to obtain compounds with high affinity and selectivity for 5-HT_1A receptor over the α₁-adrenoceptor. A series of isomeric 4-amino-2-[3-[4-(2-methoxy or nitro phenyl)-1-piperazinyl]propyl]-5-(substitutedphenyl)-2,4-dihydro-3H[1,2,4]triazole-3-thiones 12a–r was also isolated and characterized. New compounds were tested to evaluate their affinity for 5-HT_1A receptor and α₁-adrenoceptor in radioligand binding experiments. As a general trend, triazoles 11a–t showed a preferential affinity for the 5-HT_1A receptor whereas isomeric 2,4-dihydro-3H[1,2,4]triazole-3-thiones 12a–r preferentially bind to the α₁-adrenoceptor site. Several molecules showed affinities in the nanomolar range and 4-amino-3-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-5-(4-propyloxy-phenyl)[1,2,4]triazole (11o) was the most selective derivative for the 5-HT_1A receptor (K_i α₁/K_i 5-HT_1A