RESUMO
Conformationally constrained perhydroquinoxalines 4 show high κ receptor affinity, selectivity over related receptors and full agonistic activity. Since the κ affinity can be correlated with the dihedral angle of the ethylenediamine pharmacophore (4a: 55°/71°), the dihedral angles of the postulated cyclopentane derivative 5a (73°/84°) and indane derivative 6a (77°/81°) were calculated. The first step of the synthesis represents a double Henry reaction of 1,4-dialdehydes 8 and 10 with nitromethane, leading predominantly to the trans,trans-configured nitrodiols 9 and 11. X-ray crystal structure analyses of 9 and 11 led to dihedral angles O2 N−C−C−OH of 73.4 and 88.3°, respectively, which reflect the calculated dihedral angles of the hypothesized final products 5a and 6a.
Assuntos
Aldeídos/química , Analgésicos Opioides/síntese química , Desenho de Fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Analgésicos Opioides/farmacologia , Cristalografia por Raios X , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Metano/análogos & derivados , Metano/química , Estrutura Molecular , Nitroparafinas/química , Ácidos Ftálicos/química , Receptores Opioides kappa/agonistas , Relação Estrutura-AtividadeRESUMO
Disrupting genes in the rat on a genome-wide scale will allow the investigation of many biological processes linked to human health. Here we used transposon-mediated mutagenesis to knock out genes in rat spermatogonial stem cells. Given the capacity of the testis to support spermatogenesis from thousands of transplanted, genetically manipulated spermatogonia, this approach paves a way for high-throughput functional genomic studies in the laboratory rat.
Assuntos
Elementos de DNA Transponíveis/genética , Técnicas de Inativação de Genes/métodos , Mutagênese , Ratos/genética , Espermatogônias/metabolismo , Células-Tronco/metabolismo , Animais , MasculinoRESUMO
A worldwide selection of more than 200 isolates of the anthropophilic dermatophyte Trichophyton rubrum were analysed using seven microsatellite markers. Fifty-five multilocus genotypes were recognized, allowing a subdivision of the species into two populations. Both populations reproduced strictly clonally, showed a different predilection on the human host (scalp vs foot) and displayed geographic differentiation. Genotypes of one population originated predominantly from Africa, whilst the second population showed a worldwide distribution excluding the African continent. Genotypic diversity was highest in the African population, despite the lower number of strains analysed, suggesting that T. rubrum is likely to have evolved in Africa. No diagnostic correlation was observed between multilocus genotypes and any of the phenotypical characteristics of the strains. The involvement of multiple strains in a single patient detected by workers using other typing methods was not supported by these microsatellite markers. Four of the developed microsatellite markers may be applied for diagnostic purposes.