title: QSAR of 2-(4-methylsulphonylphenyl)pyrimidine derivatives as cyclooxygenase-2 inhibitors: simple structural fragments as potential modulators of activity.
abstract: The cyclooxygenase-2 (COX-2) inhibitory activity of 2-(4-methylsulphonylphenyl)pyrimidine derivatives has been quantitatively analyzed in terms of Dragon descriptors. The derived QSAR models have provided rationales to explain the activity of titled derivatives. The descriptors (Me, Mp, GATS1p and GATS5p) identified in CP-MLR analysis have highlighted the role of atomic properties, such as Sanderson electronegativity and polarizability, to explain the inhibitory activity. Additionally, prevalence of aromatic ether functionality (descriptor nRORPh) and certain structural fragments (number of Me groups, C-001; number of H attached to heteroatom, H-050 and number of H attached to α-C, H-051) in a molecular structure are helpful to rationalize the COX-2 inhibitory activity of pyrimidine derivatives. The partial least square (PLS) analysis has also confirmed the dominance of information content of CP-MLR-identified descriptors for modelling the activity.
authors.affiliation: Department of Chemistry, S.K. Government College, Sikar, India. bksharma_sikar@rediffmail.com
authors.forename: B K
authors.initials: BK
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: P
authors.initials: P
authors.lastname: Pilania
authors.forename: M
authors.initials: M
authors.lastname: Shekhawat
authors.forename: Y S
authors.initials: YS
authors.lastname: Prabhakar
mesh_terms: D020650:Combinatorial Chemistry Techniques; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D016018:Least-Squares Analysis; D008956:Models, Chemical; D008962:Models, Theoretical; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011743:Pyrimidines; D051546:Cyclooxygenase 2