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

Ruchika Chakrabarty; Jyoti Rao; Aparna Anand; Abhijeet Deb Roy; Raja Roy; G Shankar; P R Dua; Anil K Saxena

doi:10.1016/j.bmc.2007.07.018

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. Epub 2007 Aug 21.

Authors

Ruchika Chakrabarty¹, Jyoti Rao, Aparna Anand, Abhijeet Deb Roy, Raja Roy, G Shankar, P R Dua, Anil K Saxena

Affiliation

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).

MeSH terms

Antipsychotic Agents / chemical synthesis*
Antipsychotic Agents / chemistry
Antipsychotic Agents / pharmacology*
Binding, Competitive
Butanones* / chemical synthesis
Butanones* / chemistry
Butanones* / pharmacology
Dopamine D2 Receptor Antagonists*
Drug Design*
Indoles* / chemical synthesis
Indoles* / chemistry
Indoles* / pharmacology
Molecular Structure
Receptors, Dopamine D1 / antagonists & inhibitors*
Serotonin 5-HT2 Receptor Antagonists*
Stereoisomerism
Structure-Activity Relationship

Substances

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
Antipsychotic Agents
Butanones
Dopamine D2 Receptor Antagonists
Indoles
Receptors, Dopamine D1
Serotonin 5-HT2 Receptor Antagonists