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.

Keywords::

• 2-(4-Methylsulphonylphenyl)pyrimidines
• COX-2 inhibitory activity
• Dragon descriptors
• combinatorial protocol in multiple linear regression (CP-MLR)
• partial least square (PLS) analysis

Acknowledgements

The authors are thankful to their Institutions for providing necessary facilities to complete this study. Drs. Alexander Tropsha and Alexander Golbraikh are thankfully acknowledged for clarifying the formulae involved in computing k, k′, r₀² and r′₀² coefficients. The anonymous referee is thanked for select references [46,49–51] in the article. CDRI communication number 8071.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.