title: P2Y1 receptor antagonists as novel antithrombotic agents.
abstract: The P2Y(1) and P2Y(12) purinergic receptors are responsible for mediating adenosine diphosphate (ADP) dependent platelet aggregation. Evidence from P2Y(1) knockout studies as well as from nucleotide-based small molecule P2Y(1) antagonists has suggested that the antagonism of this receptor may offer a novel and effective method for the treatment of thrombotic disorders. Herein, we report the identification and optimization of a series of non-nucleotide P2Y(1) antagonists that are potent and orally bioavailable.
authors.affiliation: Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, 28/2099E, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Pfefferkorn
authors.forename: Chulho
authors.initials: C
authors.lastname: Choi
authors.forename: Thomas
authors.initials: T
authors.lastname: Winters
authors.forename: Robert
authors.initials: R
authors.lastname: Kennedy
authors.forename: Liguo
authors.initials: L
authors.lastname: Chi
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Perrin
authors.forename: Gina
authors.initials: G
authors.lastname: Lu
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Ping
authors.forename: Tom
authors.initials: T
authors.lastname: McClanahan
authors.forename: Richard
authors.initials: R
authors.lastname: Schroeder
authors.forename: Michael T
authors.initials: MT
authors.lastname: Leininger
authors.forename: Andrew
authors.initials: A
authors.lastname: Geyer
authors.forename: Sabine
authors.initials: S
authors.lastname: Schefzick
authors.forename: James
authors.initials: J
authors.lastname: Atherton
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D013329:Structure-Activity Relationship
chemical_list: D005343:Fibrinolytic Agents; C546382:P2RY1 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate