Current location: JICS Archive > Vol. 6 > No. 3 > Articles : 4

Design and Synthesis of Coumarin Substituted Oxathiadiazolone Derivatives Having Anti-Inflammatory Activity Possibly through p38 MAP Kinase Inhibition

Y. Bansal^a, S. Ratra^a, G. Bansal^a, I. Singh^b and H.Y. Aboul-Enein^c,*

^aDepartment of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147 002, Punjab, India
^bChitkara College of Pharmacy, Chandigarh-Patiala Highway, Rajpura-140401, Patiala, Punjab, India
^cPharmaceutical and Medicinal Chemistry Department National Research Centre, Dokki, Cairo 12311, Egypt

Compounds containing oxathiadiazolone nucleus bearing substituted coumarin ring were designed and synthesized while retaining the pharmacophores required for binding with p38 MAP kinase. A four-step synthetic scheme was employed for the synthesis of 7-methoxy-4-(3΄-substituted-2΄-oxo-1΄,2΄,3΄,5΄-oxathiadiazol-4΄-yl)-coumarin. The reactions were monitored by TLC and structures of the intermediates and the target compounds were ascertained by IR, NMR, Mass spectral data. The compounds were found to possess anti-inflammatory activity comparable to indomethacin. Superimposition studies of the target compounds with the lead p38 kinase inhibitors suggested that anti-inflammatory activity of the target compounds may be due to p38 MAP kinase inhibition. It was also suggested that methoxy group on coumarin nucleus may improve the binding profile with p38 MAP kinase.

Keywords: Oxathiadiazolone, Coumarin, MAP kinase, Superimposition, Isoxazolone, Pyrazolone