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 potential neuroleptic agent

  • Bioorg Med Chem. 2007 Dec 1;15(23):7361-7. doi: 10.1016/j.bmc.2007.07.018.
Ruchika Chakrabarty  1 ,  Jyoti Rao ,  Aparna Anand ,  Abhijeet Deb Roy ,  Raja Roy ,  G Shankar ,  P R Dua ,  Anil K Saxena
Affiliations
  • 1. Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, India.
PMID: 17869521 DOI: 10.1016/j.bmc.2007.07.018
Abstract

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 D(1), D(2) and 5-HT(2A) receptor blocking activity where the ratio pK(i) (5-HT(2A)) to pK(i) (D(2)) 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).

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