M.P. Giovannoni et al. / European Journal of Medicinal Chemistry 64 (2013) 512e528
527
[3] R.D. Ye, F. Boulay, J.M. Wang, C. Dahlgren, C. Gerard, M. Parmentier,
C.N. Serhan, P.M. Murphy, International Union of Basic and Clinical Pharma-
cology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family,
Pharmacol. Rev. 61 (2009) 119e161.
[4] O. Quehenberger, E.R. Prossnitz, S.L. Cavanagh, C.G. Cochrane, R.D. Ye, Multiple
domains of the N-formyl peptide receptor are required for high-affinity ligand
binding. Construction and analysis of chimeric N-formyl peptide receptors,
J. Biol. Chem. 268 (1993) 18167e18175.
[5] I. Migeotte, E. Riboldi, J.D. Franssen, F. Grégoire, C. Loison, V. Wittamer,
M. Detheux, P. Robberecht, S. Costagliola, G. Vassart, S. Sozzani, M. Parmentier,
D. Communi, Identification and characterization of an endogenous chemo-
tactic ligand specific for FPRL2, J. Exp. Med. 201 (2005) 83e93.
[6] N. Dufton, M. Perretti, Therapeutic anti-inflammatory potential of formyl-
peptide receptor agonists, Pharmacol. Ther. 127 (2010) 175e188.
[7] F.N.E. Gavins, Are formyl peptide receptors novel targets for therapeutic
intervention in ischaemia-reperfusion injury? Trends Pharmacol. Sci. 31
(2010) 266e276.
[8] Y. Cui, Y. Le, H. Yazawa, W. Gong, J.M. Wang, Potential role of the formyl
peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer’s dis-
ease, J. Leukoc. Biol. 72 (2002) 628e635.
[9] F. Cattaneo, G. Guerra, R. Ammendola, Expression and signaling of formyl-
peptide receptors in the brain, Neurochem. Res. 35 (2010) 2018e2026.
[10] J.M. Kilby, S. Hopkins, T.M. Venetta, B. Di Massimo, G.A. Cloud, J.Y. Lee,
L. Alldredge, E. Hunter, D. Lambertm, D. Bolognesi, T. Matthews, M.R. Johnson,
M.A. Nowak, G.M. Shaw, M.S. Saag, Potent suppression of HIV-1 replication in
humans by T-20, a peptide inhibitor of gp41-mediated virus entry, Nat. Med. 4
(1998) 1302e1307.
[11] A. De Paulis, N. Montuori, N. Prevete, I. Fiorentino, F.W. Rossi, V. Visconte,
G. Rossi, G. Marone, P. Ragno, Urokinase induces basophil chemotaxis through
a urokinase receptor epitope that is an endogenous ligand for formyl peptide
receptor-like 1 and -like 2, J. Immunol. 173 (2004) 5739e5748.
[12] B.S. Edwards, C. Bologa, S.M. Young, K.V. Balakin, E.R. Prossnitz, N.P. Savchuck,
L.A. Sklar, T.I. Oprea, Integration of virtual screening with high-throughput
flow cytometry to identify novel small molecule formylpeptide receptor an-
tagonists, Mol. Pharmacol. 68 (2005) 1301e1310.
[13] S. Pieretti, A. Di Giannuario, M. De Felice, M. Perretti, G. Cirino, Stimulus-
dependent specificity for annexin 1 inhibition of the inflammatory nocicep-
tive response: the involvement of the receptor for formylated peptides, Pain
109 (2004) 52e63.
[29] G. Steiner, J. Gries, D. Lenke, Synthesis and antihypertensive activity of new 6-
heteroaryl-3-hydrazinopyridazine derivatives, J. Med. Chem. 24 (1981) 59e
63.
[30] G. Kaupp, J. Schmeyers, Solid-state reactivity of the hydrazineehydroquinone
complex, J. Phys. Org. Chem. 13 (2000) 388e394.
[31] W. Hu, H. Ralay Ranaivo, S.M. Roy, H.A. Behanna, L.K. Wing, L. Munoz, L. Guo,
L.J. Van Eldik, D.M. Watterson, Development of a novel therapeutic suppressor
of brain proinflammatory cytokine up-regulation that attenuates synaptic
dysfunction and behavioral deficits, Bioorg. Med. Chem. Lett. 17 (2007) 414e
418.
[32] E.A. Steck, R.P. Brundage, L.T. Fletcher, Pyridazine derivatives. I. Some ame-
bacidal 3-pyridazones, J. Am. Chem. Soc. 75 (1953) 1117e1119.
[33] E.R. Castleman, F.Y. Wiselogle, Studies in the pyridazine series. The absorption
spectrum of pyridazine, J. Am. Chem. Soc. 67 (1945) 60e62.
[34] A.M. Kaddah, A.M. Khalil, Reactions of 3-pyridazinones with aldehydes and
Grignard reagents, Indian J. Chem. 15B (1977) 1025e1028.
[35] M.F. Ismail, A.A. El Khamry, N.A. Shams, O.M. El Sawy, Base-catalyzed
condensation of aromatic aldehydes with 4,5-dihydro-6-methylpyridazin-
3(2H)-one, Indian J. Chem. 19B (1980) 203e205.
[36] P. Powell, M.H. Sosabowski, Preparation and reactions of some 2-thienyl- and
3-thienylpyridazinones and epyridazines, J. Chem. Res. (S) 8 (1995) 306e307.
[37] N.G. Kandile, E.A. Ahmed, Synthesis of some new pyridazinones, Acta Chim.
Hung. 127 (1990) 829e835.
[38] P.G. Baraldi, D. Preti, M.A. Tabrizi, F. Fruttarolo, G. Saponaro, S. Baraldi,
R. Romagnoli, A.R. Moorman, S. Gessi, K. Varani, P.A. Borea, N6-[(Hetero)aryl/
(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-50-N-ethylcarbox-
amido-adenosines: the first example of adenosine-related structures with
potent agonist activity at the human A2B adenosine receptor, Bioorg. Med.
Chem. 15 (2007) 2514e2527.
[39] W.G. Overend, L.F. Wiggins, The conversion of sucrose into pyridazine de-
rivatives. Part I. 3-sulfanilamido-6-methylpyridazine, J. Chem. Soc. (1947)
239e244.
[40] L. Costantino, G. Rastelli, M.C. Gamberoni, M.P. Giovannoni, V. Dal Piaz,
P. Vinello, D. Barlocco, Isoxazolo-[3,4-d]-pyridazin-7-(6H)-one as a potential
substrate for new aldose reductase inhibitors, J. Med. Chem. 42 (1999) 1894e
1900.
[41] W.J. Coates, A. McKillop, Preparation of 4-amino-3(2H)-pyridazinones by
direct amination of 3(2H)-pyridazinones with hydrazine, Heterocycles 29
(1989) 1077e1090.
[14] C.N. Serhan, S.D. Brain, C.D. Buckley, D.W. Gilroy, C. Haslett, L.A. O’Neill,
M. Perretti, A.G. Rossi, J.L. Wallace, Resolution of inflammation: state of the
art, definitions and terms, FASEB J. 21 (2007) 325e332.
[15] L. Zhang, T.J. Falla, Host defense peptides for use as potential therapeutics,
Curr. Opin. Invest. Drugs 10 (2009) 164e171.
[42] C. Biancalani, M.P. Giovannoni, S. Pieretti, N. Cesari, A. Graziano, C. Vergelli,
A. Cilibrizzi, A. Di Gianuario, M. Colucci, G. Mangano, B. Garrone, L. Polenzani,
V. Dal Piaz, Further studies on arylpiperazinyl alkyl pyridazinones: discovery
of an exceptionally potent, orally active, antinociceptive agent in thermally
induced pain, J. Med. Chem. 52 (2009) 7397e7409.
[16] A. Cilibrizzi, M.T. Quinn, L.N. Kirpotina, I.A. Schepetkin, J. Holderness, R.D. Ye,
M.J. Rabiet, C. Biancalani, N. Cesari, A. Graziano, C. Vergelli, S. Pieretti, V. Dal
Piaz, M.P. Giovannoni, 6-Methyl-2,4-disubstituted pyridazin-3(2H)-ones: a
novel class of small-molecule agonists for formyl peptide receptors, J. Med.
Chem. 52 (2009) 5044e5057.
[17] H. Forsman, C. Kalderén, A. Nordin, E. Nordling, A.J. Jensen, C. Dahlgren, Stable
formyl peptide receptor agonists that activate the neutrophil NADPH-oxidase
identified through screening of a compound library, Biochem. Pharmacol. 81
(2011) 402e411.
[43] H. Lerche, D. Koenig, T. Severin, Reactions with nitroenamines. XII. Reaction of
esters and lactones with nitroenamines, Chem. Ber. 107 (1974) 1509e1517.
[44] T. Christophe, A. Karlsson, M.J. Rabiet, F. Boulay, C. Dahlgren, Phagocyte
activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not
affected by lipoxin A4, Scand. J. Immunol. 56 (2002) 470e476.
[45] H. Forsman, E. Andréasson, J. Karlsson, F. Boulay, M.J. Rabiet, C. Dahlgren,
Structural characterization and inhibitory profile of formyl peptide receptor 2
selective peptides descending from
a PIP2-binding domain of gelsolin,
J. Immunol. 189 (2012) 629e637.
[18] M. Frohn, H. Xu, X. Zou, C. Chang, M. McElvain, M.H. Plant, M. Wong, P. Tagari,
R. Hungate, R.W. Bürli, New ‘chemical probes’ to examine the role of the
hFPRL1 (or ALXR) receptor in inflammation, Bioorg. Med. Chem. Lett. 17
(2007) 6633e6637.
[19] A. Cilibrizzi, I.A. Schepetkin, G. Bartolucci, L. Crocetti, V. Dal Piaz,
M.P. Giovannoni, A. Graziano, L.N. Kirpotina, M.T. Quinn, C. Vergelli, Synthesis,
enantioresolution, and activity profile of chiral 6-methyl-2,4-disubstituted
pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists, Bioorg.
Med. Chem. 20 (2012) 3781e3792.
[46] C. Movitz, L. Brive, K. Hellstrand, M.J. Rabiet, C. Dahlgren, The annexin I
sequence gln(9)-ala(10)-trp(11)-phe(12) is a core structure for interaction
with the formyl peptide receptor 1, J. Biol. Chem. 285 (2010) 14338e14345.
[47] A.I. Khlebnikov, I.A. Schepetkin, L.N. Kirpotina, L. Brive, C. Dahlgren,
M.A. Jutila, M.T. Quinn, Molecular docking of 2-(benzimidazol-2-ylthio)-N-
phenylacetamide-derived small-molecule agonists of human formyl peptide
receptor 1, J. Mol. Model. 18 (2012) 2831e2843.
[48] F. Deflorian, K.A. Jacobson, Comparison of three GPCR structural templates for
modeling of the P2Y12 nucleotide receptor, J. Comput. Aided Mol. Des. 25 (4)
(2011) 329e338.
[49] I.A. Schepetkin, L.N. Kirpotina, A.I. Khlebnikov, M. Leopoldo, E. Lucente,
E. Lacivita, P. De Giorgio, M.T. Quinn, 3-(1H-Indol-3-yl)-2-[3-(4-nitrophenyl)
ureido]propanamide enantiomers with human formyl-peptide receptor
agonist activity: molecular modeling of chiral recognition by FPR2, Biochem.
Pharmacol. 85 (3) (2013) 404e416.
[20] Y. Sogawa, T. Ohyama, H. Maeda, K. Hirahara, Formyl peptide receptor 1 and 2
dual agonist inhibits human neutrophil chemotaxis by the induction of chemo-
attractant receptor cross-desensitization, J. Pharmacol. Sci. 115 (2011) 63e68.
[21] R.S. Reddy, K. Saravanan, P. Kumar, An efficient approach to g-alkylidene g-
butyrolactones: application to the syntheses of pyridazinones and diazo-
cinones, Tetrahedron 54 (1998) 6553e6564.
[22] J. Druey, Pyridazine in der Arzneimittelsynthese, Angew. Chem. 70 (1958) 5e13.
[23] M. Barberis, L. Pérez-Prieto, Enantioselective synthesis of sabina ketone, Tet-
rahedron Lett. 44 (2003) 6683e6685.
[24] H. Shinkai, H. Ozeki, T. Motomura, T. Ohta, N. Furukawa, I. Uchida, 4-(trans-4-
Methylcyclohexyl)-4-oxobutyric acid (JTT-608). A new class of antidiabetic
agent, J. Med. Chem. 41 (1998) 5420e5428.
[50] J.S. Mills, H.M. Miettinen, D. Cummings, A.J. Jesaitis, Characterization of the
binding site on the formyl peptide receptor using three receptor mutants and
analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu, J. Biol. Chem. 275 (2000)
39012e39017.
[51] H. Fujita, T. Kato, N. Watanabe, T. Takahashi, S. Kitagawa, Stimulation of hu-
man formyl peptide receptors by calpain inhibitors: homology modeling of
receptors and ligand docking simulation, Arch. Biochem. Biophys. 516 (2011)
121e127.
[52] C. Dahlgren, T. Christophe, F. Boulay, P.N. Madianos, M.J. Rabiet, A. Karlsson,
The synthetic chemoattractant Trp-Lys-Tyr-Met-Val-DMet activates neutro-
phils preferentially through the lipoxin A4 receptor, Blood 95 (2000) 1810e
1818.
[53] I.A. Schepetkin, L.N. Kirpotina, A.I. Khlebnikov, M.T. Quinn, High throughput
screening for small-molecule activators of neutrophils: identification of
novel N-formyl peptide receptor agonists, Mol. Pharmacol. 71 (2007)
1061e1074.
[25] S. Singh, M. Verma, K.N. Singh, Superoxide ion induced oxidation of
to -ketocarboxylic acids in aprotic medium, Synth. Commun. 34 (2004)
4471e4475.
g-lactones
g
[26] C. Grundmann, Über sulfanilamido-pyridazine (heterocyclische sulfonamide,
I. Mitteil), Chem. Ber. 81 (1948) 1e11.
[27] N. Gouault, J.F. Cupif, S. Picard, A. Lecat, M. David, Synthesis of diverse 4,5-
dihydro-3(2H)-pyridazinones on Wang resin, J. Pharm. Pharmacol. 53
(2001) 981e985.
[28] P.S. Banerjee, P.K. Sharma, R.K. Nema, Synthesis and anticonvulsant activity of
pyridazinone derivatives, Int. J. Chem. Tech. Res. 1 (2009) 522e525.