The prevalence of allergic diseases has been continuously increasing over the past few decades, affecting approximately 20–30% of the global population. Allergic reactions to infection of respiratory tract, digestive tract, and skin system involve multiple different targets. The main difficulty of anti-allergy research is how to develop drugs with good curative effect and less side effects by adopting new multi-targets and mechanisms according to the clinical characteristics of different allergic populations and different allergens. This review focuses on information concerning potential therapeutic targets as well as the synthetic anti-allergy small molecules with respect to their medicinal chemistry. The structure-activity relationship and the mechanism of compound-target interaction were highlighted with perspective to histamine-1/4 receptor antagonists, leukotriene biosynthesis, Th2 cytokines inhibitors, and calcium channel blockers. We hope that the study of chemical scaffold modification and optimization for different lead compounds summarized in this review not only lays the foundation for improvement of success rate and efficiency of virtual screening of antiallergic drugs, but also can provide valuable reference for the drug design of related promising research such as allergy, inflammation, and cancer.
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