RESUMO
Virtual worlds (VWs) are computer-simulated environments which allow users to create their own virtual character as an avatar. With the rapidly growing user volume in VWs, platform providers launch virtual goods in haste and stampede users to increase sales revenue. However, the rapidity of development incurs virtual unrelated items which will be difficult to remarket. It not only wastes virtual global companies' intelligence resources, but also makes it difficult for users to find suitable virtual goods fit for their virtual home in daily virtual life. In the VWs, users decorate their houses, visit others' homes, create families, host parties, and so forth. Users establish their social life circles through these activities. This research proposes a novel virtual goods recommendation method based on these social interactions. The contact strength and contact influence result from interactions with social neighbors and influence users' buying intention. Our research highlights the importance of social interactions in virtual goods recommendation. The experiment's data were retrieved from an online VW platform, and the results show that the proposed method, considering social interactions and social life circle, has better performance than existing recommendation methods.
Assuntos
Comércio , Simulação por ComputadorRESUMO
Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARgamma) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-alkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6-7-Z-olefin on the trienoic acid moiety. The synthesis and structure-activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.
Assuntos
Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Caprilatos/química , Caprilatos/farmacologia , Tiazolidinedionas , Alcenos/química , Alcenos/farmacologia , Animais , Derivados de Benzeno/síntese química , Caprilatos/síntese química , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Desenho de Fármacos , Sinergismo Farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/antagonistas & inibidores , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Receptores X de Retinoides , Rosiglitazona , Relação Estrutura-Atividade , Tiazóis/farmacologia , Tiroxina/sangue , Fatores de Transcrição/agonistas , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção , Triglicerídeos/sangueRESUMO
A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.
Assuntos
Oxazinas/síntese química , Oxazinas/farmacologia , Quinolonas/síntese química , Quinolonas/farmacologia , Receptores Androgênicos/efeitos dos fármacos , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Indicadores e Reagentes , Masculino , Modelos Moleculares , Orquiectomia , Ratos , Receptores Androgênicos/química , Receptores de Progesterona/química , Receptores de Progesterona/efeitos dos fármacos , Receptores da Somatotropina/química , Receptores da Somatotropina/efeitos dos fármacos , Relação Estrutura-Atividade , Testosterona/sangueRESUMO
New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic increase of exposure compared to our reference compound, 3 (LG101506).