QSAR Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad- 211 002, Uttar Pradesh, India E-mail : vinay_qsar@rediffmail.com, draksrivastava1@rediffmail.com Manuscript received 29 February 2008, revised 7 April 2008, accepted 8 April 2008 Quantitative structure-activity relationship studies were performed on a series of RNA-polymerase inhibitors which show activity against Rifampicin resistant Staphylococcus aureus. Physico-chemical parameters together with indicator variable, gave the best model having significant statistical features including cross-validated parameters. Pogliani factor Q and the results of LOO (leave one out) method confirm the reliability and predictability of the proposed models and it may concluded that larger and polar groups will favour the inhibitory activity (plC50).