Asunto(s)
Dibenzocicloheptenos/síntesis química , Dibenzocicloheptenos/farmacología , Hipnóticos y Sedantes/síntesis química , Ciclización , Dibenzocicloheptenos/química , Humanos , Hipnóticos y Sedantes/química , Hipnóticos y Sedantes/farmacología , Mianserina/análogos & derivados , Mianserina/química , Mianserina/farmacología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Relación Estructura-ActividadRESUMEN
Since their discovery in 1992, 3,4-dihydro-2-alkoxy-6-benzyl-4-oxypyrimidines (DABOs) have been subjected to many structural modifications in order to obtain better non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of AIDS. Herein, we report a straightforward and versatile route for the synthesis of novel C-6 arylmethyl-functionalized S-DABO, a poorly explored class of derivatives. Finally, biological evaluation of the synthesized derivatives led to the identification of a promising anti-HIV-1 lead compound.
Asunto(s)
Fármacos Anti-VIH/síntesis química , Pirimidinas/síntesis química , Inhibidores de la Transcriptasa Inversa/síntesis química , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Estructura Molecular , Pirimidinas/química , Pirimidinas/farmacología , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacologíaRESUMEN
An ultimate and general model describing the interaction between opioid ligands and mu-opioid receptors is not available yet, so the mode of action of atypical peptide analogues or peptidomimetics is worthy of investigation. In this context, the peptide c[-Tyr-d-Pro-d-Trp-Phe-Gly-] was observed to act as an agonist toward mu-opioid receptors with appreciable potency, albeit deprived of a protonable nitrogen. This compound was synthesized as a member of a library of diastereo- or enantiomeric cyclic peptides based on the sequence of endomorphin-1, aiming to obtain lipophilic peptide ligands active at the mu-opioid receptors, having good performances in terms of resistance to enzymatic degradation and permeation of biological barriers.
