Synthesis and Biological Evaluation of 2-(4,5,6,7-Tetrahydrobenzo[c]Isoxazol-3-yl)-4H-Chromen-4-Ones

Abstract

A new series of 2-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)-4H-chromen-4-ones 5a-e were synthesized from 1-(2-hydroxyphenyl)-3-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)propane-1,3-diones 4a-e in presence of acetic acid and conc. HCl. Compounds 4a-e were synthesized by Baker-Venkataraman rearrangement from 2-acetylphenyl 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylate 3a-e in presence of pyridine and KOH and compounds 3a-e were synthesized from 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylic acid 1 and substituted 2-hydroxy acetophenone 2a-e. All the synthesized compounds were characterized with the help of IR, ¹H NMR, ¹³C NMR and mass spectroscopic techniques. All the compounds were screened for their in vitro anti-inflammatory activities. Furthermore, molecular docking study against COX-2 enzyme could provide valuable insight into the binding affinity of these molecules and the type of thermodynamic interactions governing their binding.

Graphical Abstract

Keywords:

• β-Diketones
• anti-inflammatory screening
• COX-2 enzyme
• molecular docking
• ADME

Acknowledgement

Authors are thankful to Schrödinger Inc. for providing the GLIDE program to perform the molecular docking study.

Disclosure statement

No potential conflict of interest was reported by the authors.