A Comprehensive Review of Structure–Activity Relationships of Drugs Used in Asthma and Allergic Airway Diseases

Asthma is a chronic inflammatory airway disorder characterized by bronchoconstriction, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction. The pharmacological management of asthma involves several classes of drugs, including corticosteroids, β₂-adrenergic bronchodilators, anticholinergic agents, antihistamines, and nasal decongestants. The therapeutic efficacy and safety of these agents are strongly influenced by their chemical structures. Structure–Activity Relationship (SAR) studies help in understanding how structural modifications affect receptor selectivity, potency, lipophilicity, onset and duration of action, metabolic stability, and adverse effects. Corticosteroids require a steroid nucleus with appropriate substitutions to enhance glucocorticoid activity and pulmonary selectivity. β₂-Agonists depend on aromatic substitutions, ethanolamine side chains, and lipophilic groups for bronchodilator activity and receptor selectivity. Anticholinergic bronchodilators contain quaternary ammonium groups and lipophilic aromatic rings that improve antimuscarinic action and reduce systemic absorption. Antihistamines require aromatic rings, spacer chains, and tertiary amines for H₁ receptor antagonism, while nasal decongestants depend on imidazoline or phenyl ethanolamine structures for α-adrenergic activity. Advances in SAR have enabled the development of safer and more effective anti-asthmatic agents with improved therapeutic outcomes and reduced systemic toxicity.