title: Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents.
abstract: Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
authors.affiliation: Center of Drug Discovery, College of Pharmacy, China Pharmaceutical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000077486:Ticagrelor
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077486:Ticagrelor; D000241:Adenosine