Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2

Srinivas, V. and Mohan, C. D. and Baburajeev, C. P. and Rangappa, S. and Jagadish, S. and Fuchs, J. E. and Sukhorukov, A. Yu. and Chandra and Mason, D. J. and Kumar, K. S. S. and Madegowda, M. and Bender, A. and Basappa and Rangappa, K. S. (2015) Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 25 (15). pp. 2931-2936. ISSN 1464-3405

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Abstract

In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4yl) benzod] isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl) piperazin-1-yl) methyl)-4a, 5,6,7,8,8a-hexahydro-4H-benzoe]1,2] oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 mu M) over COX1 (40.4 mu M) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy. (C) 2015 Elsevier Ltd. All rights reserved.

Item Type:	Article
Uncontrolled Keywords:	COX2; Oxazines; SCS-Bi2O3; Proinflammatory disease
Subjects:	C Chemical Science > Chemistry D Physical Science > Physics
Divisions:	Department of > Chemistry Department of > Physics
Depositing User:	Users 19 not found.
Date Deposited:	03 Jun 2019 05:41
Last Modified:	03 Jun 2019 05:41
URI:	http://eprints.uni-mysore.ac.in/id/eprint/2078

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