title: Structure-activity relationships of adenosine A3 receptor ligands: new potential therapy for the treatment of glaucoma.
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 A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) 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.
authors.affiliation: Pharmaceutical Technology Institute, Otsuka Pharmaceutical Factory, Inc. Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan. okamurtk@otsukakj.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kurogi
authors.forename: Kinji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Kimio
authors.initials: K
authors.lastname: Kiryu
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nagao
mesh_terms: D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D015195:Drug Design; D005901:Glaucoma / Q000188:drug therapy*; D000882:Haplorhini; D008024:Ligands; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D008024:Ligands; D011743:Pyrimidines; D043684:Receptor, Adenosine A3; D014230:Triazoles