Synthesis of Novel N-Substituted Tetrazolonaphthalenes: Agomelatin Analogs

Author(s): K. Venkatanarsimha Rao, Bethanamudi Prasanna.

Journal Name: Letters in Organic Chemistry

Volume 13 , Issue 9 , 2016

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Abstract:

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 NH4Cl 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 K2CO3 yielded the corresponding N-substituted tetrazolonaphthalenes 3(a–f).

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, 1H, 13C Nuclear 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.

Keywords: Agomelatine, naphthalenene, tetrazole, sodium azide, aryl chlorides.

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Article Details

VOLUME: 13
ISSUE: 9
Year: 2016
Page: [678 - 681]
Pages: 4
DOI: 10.2174/1570178613666161021120325
Price: $58

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