Title:New Route to Synthesize Fluorine Substituted Lamotrigine Drug Analogues as an Anti-Inflammatory Agent
VOLUME: 15 ISSUE: 1
Author(s):Mohammad Makki, Dina A. Bakhotmah*, Reda M. Abdel-Rahman and Fisal M. Aqlan
Affiliation:Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah
Keywords:Aminolysis, amminolysis, fluorinated 1, 2, 4-triazine, triazinone, anti-inflammatory activities, drug analogues.
Abstract:Aim and Objective: Lamotrigine antiepileptic drug, 3,5-diamino-6-(2',3'-dichlorophenyl)-1,2,4-
triazine is used to treat epilepsy and bipolar disorder, lamotrigine is also effective in treating some diabetic
neuropath. Recently, interest has focused on the synthesis of new lamotrigine analogues in view of their biocidal
effects. This investigation focused on synthesis of novel fluorine substituted lamotrigine drug analogues
using an efficient and environmental friendly process.
Materials and Methods: Synthetic route to fluorinated lamotrigine analogues was furnished by aminolysis and
ammionlysis of 6-(2'-amino-5'-fluorophenyl)-3-thioxo-1,2,4-triazin-5(2H,4H)one. The structures of the targets
compounds have been deduced upon their elemental analysis and spectral data (UV, IR, 1HNMR, 13CNMR and
Mass spectroscopy). The anti-inflammatory activities of the synthesized compounds are also evaluated.
Results: The acute anti-inflammatory activity of the synthesis fluorine substituted lamotrigine analogues was
evaluated and showed various anti-inflammatory effects at tested condition. Thus, compounds rich in fluorine
showed higher activity in comparison with compounds lethal of fluorine atoms. In addition, compound with -
COCF3 exhibited a higher activity over compounds with aromatic –CF. Furthermore, the higher number of
fluorine atoms tend to a higher number of enzyme receptors involved in the inflammatory process.
Conclusion: The present study described a simple and new route to synthesize some new fluorine substituted
lamotrigine analogues starting from 3-thioxo-1,2,4-triazin-5-one through a simple nucleophilic displacement of
SH and OH by amino groups. In addition, this study tends to search for new fluorinated lamotrigine analogues
as anti-inflammatory agents. The obtained results revealed that compounds binding to -CF3 are more active in
comparison with compound with aromatic –CF.
