RESUMEN
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
Asunto(s)
Benceno/química , Anciano , Animales , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCIDRESUMEN
This paper examines inequalities in the self-reported health of men and women from white and minority ethnic groups in the UK using representative data from the Health Survey for England, 1993-1996. The results show substantially poorer health among all minority ethnic groups compared to whites of working-age. The absence of gender inequality in health among white adults contrasts with higher morbidity for many minority ethnic women compared to men in the same ethnic group. The analysis addresses whether socio-economic inequality is a potential explanation for this pattern of health inequality using measures of educational level, employment status, occupational social class and material deprivation. There are marked socio-economic differences according to gender and ethnic group: high morbidity is concentrated among adults who are most socio-economically disadvantaged, notably Pakistanis and Bangladeshis. Logistic regression analyses show that socio-economic inequality can account for a sizeable proportion of the health disadvantage experienced by minority ethnic men and women, but gender inequality in minority ethnic health remains after adjusting for socio-economic characteristics.