Asunto(s)
Descubrimiento de Drogas/tendencias , Industria Farmacéutica/tendencias , Investigación/tendencias , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Animales , Minería de Datos , Bases de Datos Factuales , Aprobación de Drogas , Sistemas de Liberación de Medicamentos/tendencias , Descubrimiento de Drogas/métodos , Industria Farmacéutica/métodos , Ensayos de Selección de Medicamentos Antitumorales , Genómica , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Ratones , Relación Estructura-ActividadRESUMEN
The synthesis and biological evaluation of a series of oxindole beta(3) adrenergic receptor agonists is described. A modulation of rat atrial tachycardia was observed with substitution at the 3-position of the oxindole moiety.
Asunto(s)
Agonistas de Receptores Adrenérgicos beta 3 , Agonistas Adrenérgicos beta/síntesis química , Agonistas Adrenérgicos beta/farmacología , Indoles/síntesis química , Indoles/farmacología , Taquicardia/tratamiento farmacológico , Agonistas Adrenérgicos beta/química , Animales , Células CHO , Cricetinae , Cricetulus , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Indoles/química , Estructura Molecular , Oxindoles , Ratas , Ratas Long-Evans , Receptores Adrenérgicos beta 3/biosíntesis , Receptores Adrenérgicos beta 3/genéticaRESUMEN
Analogs to a series of D-phenylglycinamide-derived factor Xa inhibitors were discovered. It was found that the S4 amide linkage can be replaced with an ether linkage to reduce the peptide character of the molecules and that this substitution leads to an increase in binding affinity that is not predicted based on modeling. Inhibitors which incorporate ether, amino, or alkyl S4 linkage motifs exhibit similar levels of binding affinity and also demonstrate potent in vitro functional activity, however, binding affinity in this series is strongly dependent on the nature of the S1 binding element.
Asunto(s)
Anticoagulantes/farmacología , Inhibidores del Factor Xa , Glicina/análogos & derivados , Inhibidores de Serina Proteinasa/farmacología , Anticoagulantes/química , Cristalografía por Rayos X , Etanolaminas , Glicina/química , Modelos Moleculares , Péptidos/química , Inhibidores de Serina Proteinasa/químicaRESUMEN
The synthesis and biological evaluation of a series of benzimidazolone beta(3) adrenergic receptor agonists are described. A trend toward the reduction of rat atrial tachycardia upon increasing steric bulk at the 3-position of the benzimidazolone moiety was observed.