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Therefore, FPRs represent an important therapeutic target for the treatment of both cancer and inflammatory diseases. Previously, we identified selective or mixed FPR agonists with pyridazinone or pyridinone scaffolds showing a common 4\u2010(bromophenyl)acetamide fragment, which was essential for activity. We report here new pyrazole and pyrazolone derivatives as restricted analogues of the above 6\u2010membered compounds, all exhibiting the same 4\u2010bromophenylacetamide side chain. Most new products had low or absent FPR agonist activity, suggesting that the pyrazole nucleus was not appropriate for FPR agonists. This hypothesis was confirmed by molecular modeling studies, which highlighted that the five\u2010membered scaffold was responsible for a worse arrangement of the molecules in the receptor binding site.<\/jats:p>","DOI":"10.1111\/cbdd.13913","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T11:01:55Z","timestamp":1624186915000},"page":"582-603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis, biological evaluation, molecular modeling, and structural analysis of new pyrazole and pyrazolone derivatives as N\u2010formyl peptide receptors agonists"],"prefix":"10.1111","volume":"98","author":[{"given":"Claudia","family":"Vergelli","sequence":"first","affiliation":[{"name":"Neurofarba Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei I.","family":"Khlebnikov","sequence":"additional","affiliation":[{"name":"National Research Tomsk Polytechnic University Tomsk Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia","family":"Crocetti","sequence":"additional","affiliation":[{"name":"Neurofarba Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-7965","authenticated-orcid":false,"given":"Gabriella","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neurofarba Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niccol\u00f2","family":"Cantini","sequence":"additional","affiliation":[{"name":"Neurofarba Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliya N.","family":"Kirpotina","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Montana State University Bozeman MT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor A.","family":"Schepetkin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Montana State University Bozeman MT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Cilibrizzi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science King\u2019s College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Montana State University Bozeman MT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Paoli","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering University of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Paola","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"Neurofarba Pharmaceutical and Nutraceutical Section University of Florence Sesto Fiorentino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.22.207"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.01.055"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u2010291X(90)91143\u2010G"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.007"},{"key":"e_1_2_9_6_1","volume-title":"Bruker APEX2","author":"Bruker","year":"2012"},{"key":"e_1_2_9_7_1","volume-title":"Bruker SAINT","author":"Bruker","year":"2012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.04.068"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22162"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm900592h"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.04.043"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308253110"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.06.036"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217815"},{"key":"e_1_2_9_16_1","unstructured":"Dal Piaz V. 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