Synthesis and preliminary pharmacological evaluation of imidazo[2,1-f]purine-2,4-dione derivatives

详细信息    查看全文

• 作者：Agnieszka Zagó ; rska ; Sł ; awomir Jurczyk ; Maciej Pawł ; owski ; Mał ; gorzata Dybał ; a ; Gabriel Nowak ; Ewa Tatarczyń ; ska ; Agnieszka Nikiforuk ; Ewa Chojnacka-Wó ; jcik
• 关键词：Theophylline ; Imidazo[2 ; 1-f]theophyllines ; Arylalkylpiperazines ; 5-HT_1A ; 5-HT_2A ; D₁ ; D₂ receptor affinities ; Anxiolytics/antidepressants
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 2009
• 年：2009
• 卷：44
• 期：11
• 页码：4288-4296
• 全文大小：287 K

文摘

A series of N-8-arylpiperazinylpropyl derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2–10) and amide derivatives of 1,3-dimethyl-6,7-dihydroimidazo[2,1-f]purine-2,4-(1H,3H)-dione-7-carboxylic acid (11–13) were synthesized. Compounds (2–10) evaluated in vitro were potent 5-HT_1A receptor ligands. Preclinical studies indicated that 8-[3-(N4-phenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2) exerts anxiolytic-like activity in the four-plate test in mice; however its effect was weaker, than that produced by Diazepam. This compound and 8-[3-(N4-2′-metoxyphenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (3) behaved like antidepressants in the forced swimming test in mice; and their activity in that model was comparable with the effect of Imipramine. The obtained results suggested that the long-chain arylpiperazines (LCAPs) linked to tricyclic derivatives of the theophylline remain a worthy of future research for obtaining new derivatives with potential anxiolytic/antidepressant activity.