ABSTRACT
En el presente estudio se determinó la cantidad de productos sub estándar según la clasificación descrita en la ley 29459: "Ley de los productos farmacéuticos, dispositivos médicos y productos sanitarios", analizados en el Centro Nacional de Control de Calidad del Instituto Nacional de Salud-Perú (CNCC), durante el periodo 2015-2019
Subject(s)
Quality Control , Biological Products , Pharmaceutical PreparationsABSTRACT
New series of 2-(4-methylsulfonylphenyl) and 2-(4-sulfamoylphenyl)pyrimidines were synthesized and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). COX-1 and COX-2 inhibitory activity of these compounds was determined using purified enzyme (PE) and human whole blood (HWB) assays. Extensive structure-activity relationship (SAR) work was carried out within these series, and a wide number of potent and specific COX-2 inhibitors were identified (HWB COX-2 IC(50)=2.4-0.3nM and 80- to 780-fold more selective than rofecoxib).
Subject(s)
Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Sulfur Compounds/chemical synthesis , Sulfur Compounds/pharmacology , Cyclooxygenase 2 Inhibitors/chemistry , Inhibitory Concentration 50 , Methylation , Molecular Structure , Pyrimidines/chemistry , Structure-Activity Relationship , Sulfur Compounds/chemistryABSTRACT
A concise synthesis of a series of novel dibenzoxepino[4,5-d]pyrazoles was accomplished by implementation of an intramolecular Ullmann-ether reaction on o,o'-halohydroxy-4,5-diarylpyrazoles mediated by CuBr.DMS. An alternative useful approach based on the palladium-catalyzed biaryl-ether linkage formation (Buchwald-Hartwig reaction) was also successfully applied, offering limitations with regard to the steric demand of the substituents. The synthesis of the key o,o'-halohydroxy-4,5-diarylpyrazole intermediates proceeds through the construction of the heterocyclic ring by a tandem amine-exchange/heterocyclization sequence of 3-N,N-(dimethylamino)-1,2-diarylpropenones with phenylhydrazine followed by basic hydrolysis for deprotection. The enamino ketone precursors were conveniently prepared from the corresponding O-sulfonyloxy and O-benzoyloxy ortho-substituted 1,2-diarylethanones, starting from inexpensive salicylaldehyde or phenylacetic derivatives. Preliminary binding affinity experiments against peripheral and central nervous system receptors have been done with negative results.
