The antiepileptic lamotrigine and its analogues: Comparative theoretical electronic properties

Electronic properties of lamotrigine (LTG) and two analogues (A1 and A2) ar e compared through MOPAC-AM1 calculations. Two stable conformers of LTG are calculated to exist in agreement with X-ray crystallography. In the three compounds and the two conformers for each of them, the more favorable proto nation sites are N-2 and N-4; these should then be the sites appropriate fo r interaction with a receptor, and group valence reinforces the supposition . The molecular electrostatic potentials show that a region between the two chlorine atoms in LTG could be the site for an electrostatic interaction w ith a corresponding site in the receptor. The fluorine atom in A1 would pla y an equivalent role. A simple model for LTG-receptor interaction is propos ed.