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

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

Journal

Bioorganic & Medicinal Chemistry Letters
ISSN: 1464-3405 , E-ISSN: 0960-894X

Output data

Year: 2015, Volume: 25, Number: 15, Pages: 2931-2936 Pages count : 6 DOI: 10.1016/j.bmcl.2015.05.047

Authors

Srinivas V. ¹ , Mohan Chakrabhavi Dhananjaya ² , Baburajeev C.P. ¹ , Rangappa Shobith ³ , Jagadish Swamy ² , Fuchs Julian E. ⁴ , Sukhorukov Alexey Yu. ⁵ , Chandra n ⁶ , Mason Daniel J. ⁴ , Sharath Kumar Kothanahally Shivaramu ² , Madegowda Mahendra ⁶ , Bender Andreas ⁴ , Basappa n ¹ , Rangappa Kanchugarakoppal Subbegowda ²

Affiliations

1	Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India
2	Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysore 570006, India
3	Frontier Research Center for Post-genome Science and Technology, Hokkaido University, Sapporo 060-0808, Japan
4	Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom
5	N.D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, 47, Moscow 119991, Russia
6	Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore 570006, India

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-4-yl)benzo[d]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-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.

Srinivas V. , Mohan C.D. , Baburajeev C.P. , Rangappa S. , Jagadish S. , Fuchs J.E. , Sukhorukov A.Y. , Chandra n. , Mason D.J. , Sharath Kumar K.S. , Madegowda M. , Bender A. , Basappa n. , Rangappa K.S.
Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2
Bioorganic & Medicinal Chemistry Letters. 2015. V.25. N15. P.2931-2936. DOI: 10.1016/j.bmcl.2015.05.047 WOS Scopus OpenAlex

Web of science:	WOS:000356101700011
Scopus:	2-s2.0-84930930914
OpenAlex:	W425532948

DB	Citing
OpenAlex	43
Scopus	44
Web of science	41