Docking studies of 3-carboxamides benzothiazines 1,1-dioxide derivatives with COX II

JAVIER GRIS, MARTÍN DRAGONETTI, BEATRIZ FERNÁNDEZ, ALBERTINA MOGLIONI AND

Istambul, Turquía

Congreso; XIX International Symposium on Medicinal Chemistry; 2006

In 1996 meloxicam outstood and was commercialized due to its 8 times greater selectivity to COX-2. Last year some compounds of the Coxibs family were retired from the pharmaceutical market due to adverse events detected. Since this event the oxicams family selective to COX II should be considered again as a potential candidate to develop new leaders in this therapeutic area. Due that no oxicams-COX complex cristallographies could be achieved until now, this work tries to explain as a first approach the chemical-molecular basis of action and selectivity of oxicams to COX II, performing a computational docking of Piroxicam (non selective to COX II) and meloxicam (selective to COX II) with the COX II using the FlexX-Pharm program. The crystallographic data of the complexes of SC-558-COX-2 (6 COX) were obtained from the Protein data bank [2]. The definition of the starting model of the active site and active site surface were performed by the FlexX-Pharm program with a 7.5 Å radius. As a result of the docking of the meloxicam-COX II. From this observations meloxicam analogues were planned tending to a major selectivity towards COX II. They are being syntethised and will be pharmacologically evaluated to confirm the stated predictions.