P2Y1 receptor antagonists as novel antithrombotic agents.
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.
Pfefferkorn
Jeffrey A
JA
Pfizer Global Research & Development, Michigan Laboratories, 2800 Plymouth Road, 28/2099E, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com
Choi
Chulho
C
Winters
Thomas
T
Kennedy
Robert
R
Chi
Liguo
L
Perrin
Lisa A
LA
Lu
Gina
G
Ping
Yun-Wen
YW
McClanahan
Tom
T
Schroeder
Richard
R
Leininger
Michael T
MT
Geyer
Andrew
A
Schefzick
Sabine
S
Atherton
James
J
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
D005343:Fibrinolytic Agents; C546382:P2RY1 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate