In connection to developing non-steroidal estrogen analogs, the present study explores the pharmacophore of triphenylacrylonitriles (Fig. 1) for binding affinity to estrogen receptor using Electrotopological State (E-State) indices of constituting atoms. The analysis shows the efficacy of E-State index in developing statistically acceptable model, which defines the electronic environment and topological states of diverse atoms in a molecule. The investigation concluded that electrophilic substitutions at C6 and C18 of the phenyl rings (A and C rings respectively) attached to C2 and C1 of ethylenic moiety, along with presence of hydroxyl substitution at C12 (ring B) and no. of non-hydrogen free terminal atoms of the molecule have influence on the binding affinity to the estrogen receptor.