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

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Abstract

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.

Structure–activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c]pyrimidines (1, 2, and 3) were performed.

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Acknowledgments

We thank Dr. Yasuhide Inoue, Dr. Akira Momii, Mr. Hiroshi Fujiwara, and Mr. Eric Hasegawa (Otsuka Pharmaceutical Factory, Inc.) for their support of this effort.

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Present address: Cambridge Isotope Laboratories, 50 Frontage Road, Andover, MA 01810, USA.

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