RESUMEN
A series of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines (1) and (2) were synthesized and evaluated for their antimicrobial activity against three representative gram-positive bacteria and two fungi. The structure-activity relationship (SAR) demonstrates that the 3- or 4-fluorophenyl component attached directly to the triazine ring was essential for activity. Of these compounds, 14, 15, and 25 demonstrated significant activity against all selected organisms compared to control. These compounds were generally nontoxic and may prove useful as antimicrobial agents.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Triazinas/síntesis química , Triazinas/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/fisiología , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
[reaction: see text] A copper-catalyzed asymmetric addition of diorganozinc reagents to N-phosphinoylimines has been developed for the synthesis of chiral alpha,alpha,alpha-trifluoromethylamines. The trifluoromethyl ketimines, generated in situ from the corresponding hemiaminals, led to the chiral amides in high yields (71-89%) and excellent enantiocontrol (91-99% ee).
RESUMEN
A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.
Asunto(s)
Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/farmacología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Proteína Estafilocócica A/metabolismo , Triazinas/síntesis química , Triazinas/farmacología , Animales , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/metabolismo , Materiales Biomiméticos/química , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Riñón/efectos de los fármacos , Riñón/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Ratones , Modelos Moleculares , Estructura Molecular , Conformación Proteica , Proteína Estafilocócica A/inmunología , Relación Estructura-Actividad , Triazinas/químicaRESUMEN
[reaction: see text] The synthesis of N-diphenylphosphinoylimines involving the treatment of aldehydes with P,P-diphenyl N-sulfinylphosphoramidate (Ph2P(O)NSO) is described. The reagent is prepared from P,P-diphenylphosphinic amide, thionyl chloride, and imidazole.
Asunto(s)
Iminas/síntesis química , Ácidos Fosfínicos , SolventesRESUMEN
A new class of orthoacylimine-derived chiral auxiliaries has been synthesized and tested in the nucleophilic addition of organolithium reagents to imines. The precursors can be prepared by an aza-Wittig reaction between the corresponding orthoacyl azide and a variety of aldehydes in the presence of trialkylphosphines. The nucleophilic addition of organolithium reagents led to the addition products in good yields and with good to excellent diastereoselectivities (from 85:15 to 99:1). The chiral, nonracemic secondary amines could be readily obtained under mild hydrolytic condition. Furthermore, the chiral auxiliary can be recovered in quantitative yield and reconverted to the starting orthoacyl azide precursor. This method was applied to the synthesis of (S)-t-leucine.