Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Srinivas, V.; Mohan, Chakrabhavi Dhananjaya; Baburajeev, C.P.; Rangappa, Shobith; Jagadish, Swamy; Fuchs, Julian E.; Sukhorukov, Alexey Yu.; Chandra, ; Mason, Daniel J.; Sharath Kumar, Kothanahally Shivaramu; Madegowda, Mahendra; Bender, Andreas; Basappa, ; Rangappa, Kanchugarakoppal Subbegowda
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 15(2015)
• Page Start: 2931
• Page End: 2936
• Publication Date: 2015-08-01
• Subjects: COX2 -- Oxazines -- SCS-Bi2O3 -- Proinflammatory disease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.047
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In the present study, we used solution combustion synthesis-bismuth oxide (Bi2 O3 ) as catalyst for the simple and efficient synthesis of 1, 2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[ d ]isoxazoles, 1-arylpiperazine and carbazoles. (4a R, 8a R )-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a, 5, 6, 7, 8, 8a-hexahydro-4 H -benzo[ e ][1, 2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 μM) over COX1 (40.4 μM) 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.