Structure–activity relationships of adenosine A3 receptor ligands: new potential therapy for the treatment of glaucoma

Structure–activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A3 receptor binding affinity and A3-selectivity against other subtypes. Potent and selective A3 receptor antagonists were identified and were evaluated in a monkey model of intraocular pressure by eye-drop administration. As a result, compound 1c (OT-7999) was found to significantly decrease intraocular pressure in the animal model.