RESUMO
A chiral chromatography method enabling the simultaneous diastereo- and enantioseparation of N(α)-Boc-N(4)-(hydroorotyl)-4-aminophenylalanine [Boc-Aph(Hor)-OH, 1] was optimized with a quinine-based zwitterionic stationary phase. The polar-ionic eluent system consisting of ACN:MeOH:water-49.7:49.7:0.6 (v/v/v) with formic acid (4.0mM) and diethylamine (2.5mM), allowed the successful separation of the four acid stereoisomers: αd,d-/d,l-1=1.08; αd,l-/l,d-1=1.08; αl,d-/l,l-1=1.40. According to the in-house developed synthetic procedure and the recorded electronic circular dichroism spectra, the following stereoisomeric elution order was readily established in the optimal chromatographic conditions: d,d-1Assuntos
Aminoácidos/isolamento & purificação
, Fenilalanina/análogos & derivados
, Quinina/química
, Aminoácidos/química
, Cromatografia Líquida de Alta Pressão
, Cromatografia por Troca Iônica
, Cinchona/química
, Dietilaminas/química
, Formiatos/química
, Simulação de Dinâmica Molecular
, Fenilalanina/química
, Fenilalanina/isolamento & purificação
, Estereoisomerismo
RESUMO
N-Aryl-5-aminopyrazole represents a key structural motif in a plethora of biologically active molecules endowed with a wide spectrum of pharmacological properties. Accordingly, this scaffold can be certainly included in the category of a privileged structure. As an example, N-aryl-5- aminopyrazole along with its 5-ureido derivatives are recurrent scaffolds in the field of inhibition of the different members of mitogen-activated protein kinases (MAPKs). Over the past recent years a large number of papers highlighting the design, synthesis and biological evaluation of different classes of N-aryl-5-aminopyrazole-containing compounds have been reported in the literature, but a review on this topic is still missing. With the aim to fill this gap, the present review article focuses on the recent developments (1995-mid2014) on the application of the N-aryl-5-aminopyrazole-based compounds in different therapeutic fields, with a particular attention to the design and structure-activity relationships (SAR) aspects of each class of compounds.