A novel pyridazinone derivative as a nonprostanoid PGI2 agonist.
A novel optically pure pyridazinone derivative was synthesized and identified as a nonprostanoid PGI2 agonist. It inhibited ADP-induced aggregation of human platelets with an IC50 value of 0.081 microM and has high oral bioavailability (56%) with a long half-life (4.3 h) in rats.
Tsubaki
K
K
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Taniguchi
K
K
Tabuchi
S
S
Okitsu
O
O
Hattori
K
K
Seki
J
J
Sakane
K
K
Tanaka
H
H
D000085:Acetates / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D011464:Epoprostenol / Q000819:agonists*; D005260:Female; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000819:agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011724:Pyridazines / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000085:Acetates; C424129:FR 181877; D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D000244:Adenosine Diphosphate; D011464:Epoprostenol