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Biomedical subjects

R G Sherrill

Publications and source records attributed to R G Sherrill.

8 recordsLinked to original sources
PubMed1992

(Aminoalkoxy)chromones. Selective sigma receptor ligands.

A series of (aminoalkoxy)chromones has been prepared, members of which bind potently (16-100 nM) at the sigma binding site and bind weakly (greater than 1000 nM) at the dopamine D2 receptor and 33 other receptors, second messenger systems, and ion channels. At the sigma receptor, the preferred position of attachment for the aminoalkoxy side chain to the chromone ring followed the rank order: 7-position greater than 5-position greater than 6-position. Chromones that contained a 2-substituent that was not coplanar with the chromone ring system showed improved binding over compounds with coplanar substituents. The most potent compound at the sigma site, 7-[[7-(4-hydroxypiperidyl)heptyl]oxy]-2-phenylchromone (74), had receptor affinities (IC50) of 16 nM at the [3H]DTG site, 19 nM at the [3H]-(+)-3-PPP site, and 4000 nM (Ki) at the dopamine D2 receptor. The most selective compound examined, 6-[[6-(4-hydroxypiperidyl)hexyl]-oxy]-2-cyclopentylchromone (58), exhibited IC50s of 51 nM at the [3H]DTG site, 55 nM at the [3H]-(+)-3-PPP site, and 21,000 nM (Ki) at the dopamine D2 receptor. Compound 44 (6-[[6-(4-hydroxypiperidyl)hexyl]oxy]-3-methylflavone, NPC 16377) was systemically effective (ip and po) in two behavioral models predictive of antipsychotic compounds and systemically active in animal models of ischemia.

Chromones↗
PubMed1992

Primary causes of medical instability of Medicare patients at discharge 1990-1991.

BACKGROUND: HCFA-sponsored Peer Review Organizations nationwide have been criticized by organized medicine, Medicare beneficiaries and interested Congressional parties for being punitive without exploiting educational opportunities garnered through their massive data collection capabilities. Until now this data has been poorly analyzed and has not been adequately utilized as a positive motivational tool. METHODS: HCFA has developed, with the cooperation of the medical community, six generic screens for Peer Review Organizations to utilize when evaluating quality care provided Medicare beneficiaries in an acute care setting. Through the sheer volume of cases seen, significant inpatient information can be obtained that cannot be duplicated in any other epidemiological endeavor. Line item discrepancies can be further studied through small-area-analysis to determine "who" as well as "what" may be the problem. RESULTS: By compiling and reviewing data in a systematic manner over two years (1990-1991), the Alabama Quality Assurance Foundation (AQAF) has singled out problems with patient medical stability at discharge as the predominant concern for care providers and reviewers alike. CONCLUSIONS: Having determined the primary problem in rendering quality care in a Prospective Payment System to Medicare beneficiaries lies in premature discharges, subsequent small-area-analysis further narrows the focus of concerned individuals. Hopefully, practitioners and providers alike will act on their own initiative in correcting this problem. Follow-up review will be utilized to assure this self-corrective action.

Alabama↗
PubMed1991

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives.

A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4 microM, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

Antiviral Agents↗
PubMed1991

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2.

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells. The exceptions were replacement of the urea oxygen with sulfur or selenium to give the corresponding thio- or selenoureas. These were found to be more active than the oxygen counterparts. A small series of analogues was synthesized and tested which allowed direct comparison of urea and thiourea derivatives. Without exception, the latter were always more active than the former. The most active compound of this series (8d) was found to inhibit the HIV-1 virus with an IC50 of 0.012 microM which is comparable to that of AZT.

Antiviral Agents↗