Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two most effective compounds described and molecular modeling study on their interactions with phosphodiesterase 3A catalytic site.

Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE

Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-

3',5'-Cyclic-AMP Phosphodiesterases/*antagonists & inhibitors ; Coumarins/*chemical synthesis ; Morpholines/*chemical synthesis ; Phosphodiesterase Inhibitors/*chemical synthesis ; Piperazines/*chemical synthesis ; Platelet Aggregation Inhibitors/*chemical synthesis; 3',5'-Cyclic-AMP Phosphodiesterases/blood ; 3',5'-Cyclic-AMP Phosphodiesterases/chemistry ; Catalytic Domain ; Coumarins/chemistry ; Coumarins/pharmacology ; Cyclic Nucleotide Phosphodiesterases, Type 3 ; Humans ; In Vitro Techniques ; Models, Molecular ; Morpholines/chemistry ; Morpholines/pharmacology ; Phosphodiesterase Inhibitors/chemistry ; Phosphodiesterase Inhibitors/pharmacology ; Piperazines/chemistry ; Piperazines/pharmacology ; Platelet Aggregation Inhibitors/chemistry ; Platelet Aggregation Inhibitors/pharmacology

The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morpholinoethoxy)-substituted new analogue 5u were notably more effective inhibitors of pure human platelet PDE3 than milrinone and cilostazol: these data were related, through a molecular modeling study, with the molecular interactions of the four compounds with the human PDE3A catalytic site.

0 (8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin)
0 (8-methyl-7-(2-morpholinoethoxy)-4-(1-piperazinyl)-2H-1-benzopyran-2-one)
0 (Coumarins)
0 (Morpholines)
0 (Phosphodiesterase Inhibitors)
0 (Piperazines)
0 (Platelet Aggregation Inhibitors)
EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 3)
EC 3.1.4.17 (PDE3A protein, human)

Date Created: 20070516 Date Completed: 20070815 Latest Revision: 20141120

20231215

10.1021/jm0611511

17500510