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. 2014 Feb 17;5(5):512-6.
doi: 10.1021/ml400500e. eCollection 2014 May 8.

2-(2-Arylphenyl)benzoxazole As a Novel Anti-Inflammatory Scaffold: Synthesis and Biological Evaluation

Kapileswar Seth  1 , Sanjeev K Garg  1 , Raj Kumar  1 , Priyank Purohit  1 , Vachan S Meena  1 , Rohit Goyal  2 , Uttam C Banerjee  1 , Asit K Chakraborti  1
Affiliations

2-(2-Arylphenyl)benzoxazole As a Novel Anti-Inflammatory Scaffold: Synthesis and Biological Evaluation

Kapileswar Seth et al. ACS Med Chem Lett. .

Abstract

The 2-(2-arylphenyl)benzoxazole moiety has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The 2-(2-arylphenyl)benzoxazoles 3a-m have been synthesized by Suzuki reaction of 2-(2-bromophenyl)benzoxazole. Further synthetic manipulation of 3f and 3i led to 3o and 3n, respectively. The compounds 3g, 3n, and 3o selectively inhibited COX-2 with selectivity index of 3n much better than that of the COX-2 selective NSAID celecoxib. The in vivo anti-inflammatory potency of 3g and 3n is comparable to that of celecoxib and the nonselective NSAID diclofenac at two different doses, and 3o showed better potency compared to these clinically used NSAIDs.

Keywords: 2-(2-Arylphenyl)benzoxazoles; 3D QSAR; cyclooxygenase-2 selective; in vivo potency; novel anti-inflammatory scaffold.

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Figures

Figure 1
Figure 1
Topological model for selective COX-2 inhibition through scaffold-hopping.
Scheme 1
Scheme 1. Synthesis of 3a–m
Reagents and conditions: (a) Pd(PPh3)4 (3 mol %), Na2CO3 (1.2 equiv), DMF, reflux, 2.5–6 h.
Scheme 2
Scheme 2. Synthetic Modification of 3i and 3f to Form 3n and 3o, Respectively
Reagents and conditions: (a) Pd/C (10% ww/w), H2, 40 psi, EtOH, rt, 4 h, 80%; (b) aq. oxone (3 equiv), 1,4-dioxane, rt, 4 h, 80%.
Figure 2
Figure 2
Comparison of the COX enzyme inhibitory activity/selectivity and anti-inflammatory potency of 3g, 3n, and 3o with those of the clinically used NSAIDs 4 and 5.
See this image and copyright information in PMC

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