Background: For lost twenty years, Agomelatine, a melatonin-like antidepressant drug which
is based on a naphthalene moiety has received a huge attention. This drug molecule gets short plasma
half-life as a result of undergoing very important liver first pass effect. So in order to overcome this
drawback, we have come up with an approach which is based on the use of substituted aryl derivatives
of tetrazole scaffold to replacement of the N-acetyl side chain. We successfully designed aryl substituted
tetrazolo naphthalene 3(a-f) scaffolds, a much centered template which can be elaborated further
into agomelatine compounds.
Methods: The compound which is used in the present scheme as starting material, that is, 2-(7-
methoxynaphth-1-yl)acetonitrile 1 react with NaN3
in the presence of NH4
Cl as a catalyst in dimethyl
formamide as solvent to provide the corresponding 5-(7-Methoxynaphth-1-yl methyl)-1H-tetrazole 2,
which on reaction with aryl halides a-f in presence of K2
yielded the corresponding N-substituted
Results: Novel analogues of agomelatine 3(a-f) were synthesized from 2-(7-methoxynaphth-1-
yl)acetonitrile 1. The newly synthesized compounds were established by Infra Red, 1
Magnetic Resonance, mass spectroscopy and the data of their elemental analyses.
Conclusion: We developed a simple and efficient method for the synthesis of aryl substituted tetrazolo
naphthalene 3(a-f) scaffolds, a much centered template which can be elaborated further into
agomelatine compounds. Along with this work, further important works are under progress to get more
biological activity results.