PubMed Health⌕ Search

Biomedical subjects

E Wise

Publications and source records attributed to E Wise.

8 recordsLinked to original sources
PubMed2001

4-Hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: the effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters.

Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, we previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029, 1) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable back-up candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocyle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymatic and cellular tests) and low cellular toxicity; furthermore, several analogues exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailabilty was (S)-3-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (13-(S)). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, compound 13-(S) was chosen for further preclinical evaluation.

Animals↗
PubMed1999

Health problems and service utilization in the homeless.

This study examined the health problems and utilization patterns of homeless individuals (n = 292) seeking medical services in a small, southern community. Results showed that the medical problems for which the homeless sought treatment were often (72.6 percent) a reoccurring problem for which treatment had been previously received. The most prevalent medical problem was upper respiratory infection (47 percent), likely exacerbated by the high rate (73 percent) of cigarette smoking found among the sample. More than half (51.4 percent) of the participants had used other medical services in the past month. Despite these high rates of utilization, the homeless may, in fact, be underutilizing appropriate preventive medical services, waiting until the medical problem becomes serious before seeking treatment, and overutilizing emergency rooms for nonemergency care. Community-based services sensitive to the needs of the homeless are likely to cost communities less money while providing better services to the homeless.

Adult↗