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In summary, the design, the synthesis, and the biological
evaluation of several 2-substituted pyridazinones incor-
porating a 3-oxo-3-phenylprop-1-en-1-yl fragment at
either position 4, 5 or 6 (compounds 2) or at both posi-
tions 4 and 5 (compounds 4) have been described. This
study allowed the identification of several new highly
potent antiplatelet agents and also the establishment of
the preliminary relevant features of the SAR in these
series. Further studies are in progress in our laboratories
to exploit these results for the synthesis of a larger li-
brary of hybrid structures.
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Acknowledgments
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E.; Fraiz, N.; Yan˜ez, M.; Laguna, R.; Cano, E.; Ravin˜a,
E. Bioorg. Med. Chem. Lett. 2004, 14, 321; (e) Sotelo, E.;
The authors gratefully acknowledge support from the
research council of the Instituto de Farmacia Industrial
(IFI) of the University of Santiago de Compostela
(Spain). E. Sotelo and A. Coelho are researchers of
the Isidro Parga Pondal program (Xunta de Galicia,
Spain). C. Meyers thanks the Fund for Scientific Re-
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Fraiz, N.; Yan˜ez, M.; Terrades, V.; Laguna, R.; Cano, E.;
Ravin˜a, E. Bioorg. Med. Chem. 2002, 10, 2873; (f) Sotelo,
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Sotelo, E.; Fraiz, N.; Yan˜ez, M.; Laguna, R.; Cano, E.;
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Sotelo, E.; Maes, B. U. W.; Laguna, R.; Cano, E.;
search-Flanders (Belgium) for
(aspirant).
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13. All described compounds gave satisfactory microanalyt-
ical (C, H, N 0.4%) and spectral data (300 or 400 MHz
1H NMR and FTIR). Spectral data for representative
compounds (R2 = Ph): 5-[(1E)-3-oxo-3-phenylprop-1-en-
1-yl]-2-phenylpyridazin-3(2H)-one (2c): 1H NMR: dH
(300 MHz, DMSO-d6): 8.15 (d, J = 2.1 Hz, 1H), 8.01
(d, J = 8.9 Hz, 2H), 7.83–7.64 (m, 3H), 7.52 (d,
J = 14.9 Hz, 1H), 7.48–7.37 (m, 6H), 7.16 (d,
J = 2.1 Hz, 1H). 4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]-2-
1
phenylpyridazin-3(2H)-one (2f): H NMR: dH (400 MHz,
´
Chem. 1994, 29, 249; (h) Matyus, P.; Kosary, J.; Kasztre-
iner, E.; Makk, N.; Diesler, E.; Czako, K.; Rabloczky, G.;
´
DMSO-d6): 8.75 (d, J = 15.2 Hz, 1H), 8.10 (m, 2H), 8.02
(d, J = 4.2 Hz, 1H), 7.55 (m, 10H). 6-[(1E)-3-oxo-3-
phenylprop-1-en-1-yl]-2-phenylpyridazin-3(2H)-one (2i):
´
´
Jaszlits, L.; Horvath, E.; To¨mo¨sko¨zi, Z.; Cseh, G.;