ABSTRACT The 5-HT 2A receptor binding affinities of the 2-alkyl-4-aryl-pyrimidine fused heterocycles have been quantitatively expressed in terms of topological and molecular features. The analysis revealed that less number of rotatable bonds (descriptor RBN), a more hydrophobic nature (descriptor MLOGP) and less polar surface area (descriptor PSA) in a molecular structure will be favorable to the binding affinity. A lower positive values of descriptors PW4 (path/walk 4 -Randic shape index) and MATS2m (Moran autocorrelation -lag 2/weighted by atomic masses) and higher value of descriptor MATS1v (Moran autocorrelation -lag 1/weighted by atomic van der Waals volumes) will augment the activity. Additionally, a lower value of descriptor BEHm1 (highest eigenvalue n. 1 of Burden matrix/weighted by atomic masses), higher value of descriptor BEHp1 (highest eigenvalue n. 1 of Burden matrix / weighted by atomic polarizabilities) and a higher value of 7 th order charge index (GGI7) will be beneficiary to the activity. The derived models and participating descriptors in them have suggested that the substituents of 2-alkyl-4-aryl-pyrimidine fused heterocycles have sufficient scope for further modification
