RESUMEN
High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1=10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.
Asunto(s)
Compuestos Heterocíclicos con 3 Anillos/química , Pirimidinonas/química , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Tiofenos/química , Administración Oral , Animales , Dolor Crónico/tratamiento farmacológico , Modelos Animales de Enfermedad , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Pirimidinonas/síntesis química , Pirimidinonas/uso terapéutico , Ratas , Receptores de Glutamato Metabotrópico/metabolismo , Relación Estructura-Actividad , Tiofenos/síntesis química , Tiofenos/uso terapéuticoRESUMEN
The majority of adaptationist models and research related to parenting strategies have focused on extrinsic or population-level risk as predictors of parenting. However, some researchers have called for greater consideration of cultural factors as well as on intracultural variation in parenting. This study uses a biocultural approach to examine intracultural variation in environmental risk and parenting among the Bofi foragers in Central Africa. In particular, we examine 30 mothers' experiences of child loss as a predictor of variation in maternal involvement (proximity, holding, and affection) with their young children. Multivariate and univariate analyses indicate that child loss accounted for substantial variation in maternal behaviors and was predictive of maternal holding and the expression of physical affection. In sum, our findings indicate that intracultural variation in child loss is predictive of maternal involvement with young children and that a biocultural approach is useful in explaining this variation.
Asunto(s)
Ambiente , Relaciones Madre-Hijo/psicología , Madres/psicología , Responsabilidad Parental/psicología , República Centroafricana , Preescolar , Cultura , Femenino , Pesar , Humanos , Lactante , Conducta Materna/etnología , Conducta Materna/psicología , Relaciones Madre-Hijo/etnología , Responsabilidad Parental/etnologíaRESUMEN
A novel series of 3-substituted-8-aryl-[1,2,4]-triazolo[5,1-i]purin-5-amine analogs related to Sch 58261 was synthesized in order to identify potent adenosine A(2A) receptor antagonists with improved selectivity over the A(1) receptor, physiochemical properties, and pharmacokinetic profiles as compared to those of Sch 58261. As a result of structural modifications, numerous analogs with excellent in vitro binding affinities and selectivities were identified. Moreover, compound 27 displayed both superior in vitro and highly promising in vivo profiles.