Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity

Bruno, Olga; Schenone, Silvia; Ranise, Angelo; Bondavalli, Francesco; Filippelli, Walter; Falcone, Giuseppe; Motola, Giulia; Mazzeo, Filomena

doi:10.1016/s0014-827x(98)00109-8

Cited by 48 publications

(28 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…48 For a long time we have been carrying out the synthesis of new heterocycle derivatives as potential anti-inflammatory agents. [49][50][51][52][53] Now we have focused our interest on the identification of new molecules able to impact neutrophil activation and migration. 54 In pursuing the search for new small molecules active in this field, we functionalized with a urea moiety the 5-amino-1-(2-hydroxy-2-phenylethyl)-1H-pyrazole-4-carboxylic acid ethyl ester 3, already used as a crucial intermediate, 55 and we obtained derivatives 4a-k (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of N-Pyrazolyl-N‘-alkyl/benzyl/phenylureas: a New Class of Potent Inhibitors of Interleukin 8-Induced Neutrophil Chemotaxis

et al. 2007

Self Cite

View full text Add to dashboard Cite

Neutrophils chemotaxis is a complex multistep process that, if upregulated, causes acute inflammation and a number of autoimmune diseases. We report here the synthesis of a new N-(4-substituted)pyrazolyl-N'-alkyl/benzyl/phenylureas that are potent inhibitors of interleukin-8 (IL8)-induced neutrophil chemotaxis. The first series of compounds, obtained by functionalization with a urea moiety of the 5-amino-1-(2-hydroxy-2-phenylethyl)-1H-pyrazole-4-carboxylic acid ethyl ester 3, blocked the IL8-induced neutrophil chemotaxis, while they did not block N-formylmethionylleucylphenylalanine-mediated chemotaxis. The most active compounds, 3-benzyl- (4d), 3-(4-benzylpiperazinyl)- (4i), 3-phenyl- (4k) and 3-isopropylureido (4a) derivatives, showed an IC50 of 10, 14, 45, and 55 nM, respectively. Several different molecules were then synthesized to obtain more information for SAR study. Compounds 4a, 4d, and 4k were inactive in the binding assays on CXCR1 and CXCR2 (IL8 receptors), whereas they inhibited the phosphorylation of PTKs (protein tyrosine kinases) in the 50-70 kDa region. Moreover, in the presence of the same derivatives, we observed a complete block of F-actin rise and pseudopod formation.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of N-Pyrazolyl-N‘-alkyl/benzyl/phenylureas: a New Class of Potent Inhibitors of Interleukin 8-Induced Neutrophil Chemotaxis

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Refluxing of compound (25) with DMFDMA provided the enaminones (26), which were directly allowed to react with binucleophiles such as substituted guanidine and amino azoles (3-aminopyrazoles, 3-amino-1,2,4-triazole) to give the desired compounds (27a,b) and (28a-d), respectively, as in Scheme 8 [31,32].…”

Section: Preparation Of Heterocyclicmentioning

confidence: 99%

“…1,3-Diphenylacetone (29a) reacted with an equimolecular amount of DMFDMA to give the enaminone (30) which condensed with cyanoacetamide and with cyanothioacetamide to yield 2-oxo-and 2-thioxo-pyridine-3-carbonitrile derivatives (31). The 1,3-disubstituted acetones (29a,b) reacted with two molar equivalents of DMFDMA to give the dienaminones (32) which in turn reacted with an acetic acid ammonium acetate mixture or phosphoric acid to afford 3,5-disubstituted-pyrane-4-ones (33a,b) [33,34].…”

Section: Preparation Of Heterocyclicmentioning

confidence: 99%

Dimethylformamide dimethyl acetal as a building block in heterocyclic synthesis

Abu‐Shanab

Sherif

Mousa

2009

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

show abstract

“…1. Moreover, some metal complexes of various amino acids have also reported to possess antiinflammatory and analgesic properties (Bruno et al, 1999). Recently, El-Henawy, 2013 reported the synthesis and molecular docking studies of some novel Diclofenac derivatives containing phenylalanine moiety as selective COX-2 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Novel series of phenylalanine analogs endowed with promising anti-inflammatory activity: synthesis, pharmacological evaluation, and computational insights

et al. 2014

View full text Add to dashboard Cite

A novel series of methyl-2-(substituted benzylideneamino)-3-phenyl propionate (2a-j) derivatives have been synthesized. The title compounds (2a-j) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 200 mg/kg b.w. Compound 2e exhibited the most promising and significant anti-inflammatory profile while compounds 2b, 2h, 2i, and 2j showed moderate to good inhibitory activity at 2nd and 4th h, respectively. These compounds were also found to have considerable analgesic activity (acetic acid-induced writhing model) and antipyretic activity (yeast-induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. The synthesized compounds were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by in vitro colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 2b, 2e, 2h, 2i, and 2j exhibited selective and effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of their binding affinity, docking studies were also performed using Molegro Virtual Docker (MVD-2013, 6.0) for the title compounds. It was observed that the binding affinities calculated were in agreement with the experimental IC 50 values.

show abstract

Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity

Cited by 48 publications

References 6 publications

Synthesis and Biological Evaluation of N-Pyrazolyl-N‘-alkyl/benzyl/phenylureas: a New Class of Potent Inhibitors of Interleukin 8-Induced Neutrophil Chemotaxis

Synthesis and Biological Evaluation of N-Pyrazolyl-N‘-alkyl/benzyl/phenylureas: a New Class of Potent Inhibitors of Interleukin 8-Induced Neutrophil Chemotaxis

Dimethylformamide dimethyl acetal as a building block in heterocyclic synthesis

Novel series of phenylalanine analogs endowed with promising anti-inflammatory activity: synthesis, pharmacological evaluation, and computational insights

Contact Info

Product

Resources

About