Synthesis and evaluation of 2-tosylamino and 2-tosyliminopyrimidine derivatives as inhibitors of some leukocyte functions

• Published in: European journal of medicinal chemistry Vol. 38; no. 3; pp. 289 - 296
• Main Authors: Fernandez-Ferri, Patricia, Ubeda, Amalia, Guillén, Isabel, Lasri, Jamal, González-Rosende, M.Eugenia, Akssira, Mohamed, Sepúlveda-Arques, José
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.03.2003; Elsevier
• Subjects: 2-Tosylaminopyrimidines; 2-Tosyliminopyrimidines; Arachidonate 5-Lipoxygenase - metabolism; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Degranulation - drug effects; Cell Separation; Chemistry, Medicinal; Elastase; Humans; In Vitro Techniques; Indicators and Reagents; Leukocyte Elastase - metabolism; Leukocytes; Leukocytes - drug effects; Leukocytes - metabolism; Leukocytes - ultrastructure; Leukotriene B4 - biosynthesis; Life Sciences & Biomedicine; Lipoxygenase; Lipoxygenase Inhibitors; Magnetic Resonance Spectroscopy; Medical sciences; Neutrophils - drug effects; Neutrophils - metabolism; Neutrophils - ultrastructure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyrimidines - chemical synthesis; Pyrimidines - pharmacology; Science & Technology; Tosyl Compounds - chemical synthesis; Tosyl Compounds - pharmacology; 2-Tosyliminopyrimidines; 5-LO, 5-lipoxygenase; Ts, tosyl; DIPEA, diisopropylethylamine; Elastase; IC 50, inhibitory concentration 50; Leukocytes; DMF, dimethylformamide; Lipoxygenase; LTB 4, leukotriene B 4; 2-Tosylaminopyrimidines; elastase; lipoxygenase; ANTIINFLAMMATORY ACTIVITY; leukocytes; 2-tosyliminopyrimidines; 5-LIPOXYGENASE; 2-tosylaminopyrimidines; Human; Sulfonamide; Enzyme; Nitrogen heterocycle; Antiinflammatory agent; Benzene derivatives; Enzyme inhibitor; Guanidines; In vitro; Leukotriene B4; Structure activity relation; Arachidonate 5-lipoxygenase; Carboxamide; Pyrimidine derivatives; Oxidoreductases; Inhibition; Neutrophil; Chemical synthesis; Release
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(03)00013-8

We have studied the potential anti-inflammatory effects of 20 2-tosylamino and 2-tosyliminopyrimidine new derivatives in human neutrophils. We have evaluated their interference with some leukocyte functions and 5-lipoxygenase activity. All the compounds reduced neutrophil degranulation process at concentrations in the μM range. Besides, compounds with a phenolic substitution inhibited leukotriene B 4 biosynthesis in neutrophils and decreased the cell-free 5-lipoxygenase activity. This study demonstrates that 2-tosylamino and 2-tosyliminopyrimidine derivatives can reduce the activation of neutrophil cells which may have relevance for the modulation of the inflammatory response.