Rational design, synthesis and evaluation of (6aR^*,11bS^*)-1-(4-fluorophenyl)-4-{7-[4-(4-fluorophenyl)-4-oxobutyl]1,2,3,4,6,6a,7,11b,12,12a(RS)-decahydropyrazino[2′,1′:6,1]pyrido[3,4-b]indol-2-yl}-butan-1-one as a potent

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• 作者：Ruchika Chakrabarty ; Jyoti Rao ; Aparna An ; Abhijeet Deb Roy ; Raja Roy ; G. Shankar ; P.R. Dua ; Anil K. Saxena
• 关键词：Antipsychotic ; D₁ receptor ; D₂ receptor ; 5-HT2A receptor ; Decahydropyrazino[2′ ; 1′ ; 6 ; 1]pyrido[3 ; 4-b]indole ; Neuroleptic ; NMR ; COSY ; HMBC
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 December 2007
• 卷：15
• 期：23
• 页码：7361-7367
• 文件大小：160 K

摘要

In our pursuit to prepare a potent antipsychotic compound, a novel 1,2,3,4,6,6a,7,11b,12,12a-decahydropyrazino[2′,1′:6,1]pyrido[3,4-b]indole derivative was synthesized which incorporates the butyrophenone substructure twice. This molecule has shown D₁, D₂ and 5-HT_2A receptor blocking activity where the ratio pK_i (5-HT_2A) to pK_i (D₂) is 1.42 better than risperidone (1.15). It blocks amphetamine induced hyperactivity/stereotypy and secondary conditioned avoidance responses in rodents at lower doses than those required for the neuroleptic drugs haloperidol and centbutindole (biriperone).