RESUMEN
[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.
Asunto(s)
Antibacterianos/síntesis química , Resistencia a Medicamentos , Eritromicina/química , Josamicina/química , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
The synthesis and in vitro binding of several new arginine-containing C3aR ligands are reported. DMPK properties and functional activities of selected compounds have been evaluated. One compound is shown to be active in an in vivo model of airway inflammation after aerosol administration.
Asunto(s)
Arginina/farmacología , Activación de Complemento/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Receptores de Complemento/metabolismo , Aerosoles/administración & dosificación , Animales , Arginina/análogos & derivados , Arginina/síntesis química , Inflamación/inducido químicamente , Inflamación/patología , Ligandos , Ratones , Ratones Endogámicos BALB C , Modelos Biológicos , Unión Proteica , Proteínas Serina-Treonina Quinasas/metabolismo , Mucosa Respiratoria/patología , Relación Estructura-Actividad , Factores de TiempoRESUMEN
The synthesis and structure-activity relationships against the C3a receptor of a series of substituted aminopiperidine derivatives are reported. DMPK properties and functional activities of selected compounds are described. The compounds obtained are the first non-arginine ligands of C3aR.