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0; 95%CI 0.5 to 12.5), pain intensity (MD=-0.03; 95%CI 0.34 to 0.28) and range of motion (p0.05). Current literature lacks evidence supporting the use of cryotherapy on management of acute ankle sprain. There is an urgent call for larger high-quality randomized controlled trials. Current literature lacks evidence supporting the use of cryotherapy on management of acute ankle sprain. There is an urgent call for larger high-quality randomized controlled trials.Herein, we describe the design, synthesis, and structure-activity relations