title: 2-Aminothiazole based P2Y(1) antagonists as novel antiplatelet agents.
abstract: ADP receptors, P2Y1 and P2Y12 have been recognized as potential targets for antithrombotic drugs. A series of P2Y1 antagonists that contain 2-aminothiazoles as urea surrogates were discovered. Extensive SAR of the thiazole ring is described. The most potent compound 7j showed good P2Y1 binding (Ki=12nM), moderate antagonism of platelet aggregation (PA IC50=5.2μM) and acceptable PK in rats.
authors.affiliation: Medicinal Chemistry, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb, 311 Pennington-Rocky Hill Road, Pennington, NJ 08534, USA. Zulan.Pi@bms.com
authors.forename: Zulan
authors.initials: Z
authors.lastname: Pi
authors.forename: James
authors.initials: J
authors.lastname: Sutton
authors.forename: John
authors.initials: J
authors.lastname: Lloyd
authors.forename: Ji
authors.initials: J
authors.lastname: Hua
authors.forename: Laura
authors.initials: L
authors.lastname: Price
authors.forename: Qimin
authors.initials: Q
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Chang
authors.forename: Joanna
authors.initials: J
authors.lastname: Zheng
authors.forename: Robert
authors.initials: R
authors.lastname: Rehfuss
authors.forename: Christine S
authors.initials: CS
authors.lastname: Huang
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D006207:Half-Life; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D058921:Purinergic P2Y Receptor Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D058472:Receptors, Purinergic P2Y1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000631:Aminopyridines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D013844:Thiazoles; C004483:2-aminothiazole