Synthesis of 4,5-functionalized-2-methyl-6-(substituted aryl)-3 (2H)-pyridazinones: a new group of potent platelet aggregation inhibitors.
A series of 4,5-functionalized-2-methyl-6-(substituted phenyl)-3 (2H)-pyridazinones were synthesized and evaluated as platelet aggregation inhibitors in human platelet rich plasma (PRP). The new products generally displayed significant higher activity with respect to the corresponding unsubstituted aryl compounds. Compounds 27 and 31 appeared of particular interest, being their IC50s in the submicromolar range. Structure-activity relationships (SARs) are discussed.
Dal Piaz
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V
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
Ciciani
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G
Giovannoni
M P
MP
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines; D000242:Cyclic AMP