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The syntheses of all possible stereoisomers of desfluorinated side products of the potent antihypertensive β-blocker nebivolol are reported. A straightforward approach using a common racemic precursor was employed to obtain the desired optically active building blocks. For one series of compounds, a Sharpless asymmetric epoxidation (SAE) route yielded in a direct fashion the required compounds whereas a Mitsunobu reaction was selected to obtain the other series of compounds. This offers a flexible approach to all desfluoronebivolol side-products in order to fully characterize them.

In this prospective study conducted by 9 Public Health Offices in North Rhine Westphalia 1992 to 1994, among the analysed 4058 asylum seekers aged 1-89 years the chest radiographs showed in 444 cases old specific changes and in 48 cases active tuberculosis. This was verified microbiologically. 81% of the evaluated tuberculin skin test were positive with variations between the different countries of origin, which is significantly higher than among persons born in the Fed. Rep. of Germany. A compulsory chest radiograph shortly after arrival and controlled curative or preventive chemotherapy programmes are urgently needed.

A group of 43 optically active sodium carboxylates (11a-qq and the corresponding lactones 4 were prepared from respective phenols 8 according to Schemes I-III. Phenols 8 were synthesized from commercially available compounds according to Schemes IV-IX. A number of these HMG-CoA reductase inhibitors 11 exceeded mevinolin's activity in vitro (Tables II and III). Selected lactones 4 effectively inhibited hepatic "de novo" cholesterol synthesis in rats in vivo (Table IV). After po administration to rabbits, 4ff(11ff), 4hh, and notably 11jj reduced plasma cholesterol levels more potently than mevinolin (Table V). Whereas 4ff(11ff) displayed the slight superiority expected according to in vitro data, 4hh and 11jj were considerably more potent than expected. Each of these compounds had only moderate activity after po administration to dogs (Table VI). Compound di-11ii, a hybrid of the structural elements of probucol and HMG-CoA reductase inhibitors, after po administration to rats decreased serum lipoproteins and increased HDL/LDL ratio better than probucol (Table VII). HMG-CoA reductase inhibitor 11ll and phenolic building blocks 8, notably 8jj and 8kk, inhibited LDL oxidation in vitro (Table VIII). Chemical structure-activity relationships (Table IX) and the pharmacological profile of phenoxy-type inhibitors 11 diverged from those of known HMG-CoA reductase inhibitors.

A series of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)- enoates (-heptanoates) 1 and 2 have been prepared and tested for inhibiti 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The most potent compounds exceeded mevinolin's activity in vitro and in vivo.

Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids 2-4 have been synthesized. Extensive exploration of structure-activity relationships led to several compounds exceeding the inhibitory activity of mevinolin (1b) on HMG-CoA reductase, both in vitro and in vivo. First clinical trials with 2i (HR 780) are in preparation.

The free amino acids in eccrine sweat collected from the forearms of 20 healthy trained and 20 healthy untrained men during controlled exercise were determined quantitatively using ion exchange column chromatography. Sweat was deproteinized by adding an equal volume of 5% sulphosalicylic acid. The amino acid concentrations showed a constant qualitative pattern in sweat and large individual differences. Essential amino acids, such as isoleucine, leucine, lysine, methionine, phenylalanine, and valine were excreted in relatively small amounts. As compared to the trained men, untrained men showed statistically significantly higher concentrations in sweat for the following amino acids: Alanine, arginine, glycine, histidine, isoleucine, leucine, lysine, ornithine, phenylalanine, serine, taurine, threonine, tyrosine, and valine. No significant differences were found for citrulline, cystine, ethanolamine, and methionine. The comparison of the amino acid excretions in sweat obtained under controlled exercise and in urine showed that the amounts of amino acids excreted in sweat under controlled exercise were comparable to the losses of amino acids in urine.

Unlabelled: With the aid of ion exchange column chromatography we determined quantitatively the free amino acids in thermal sweat of the total human body surface. Sweat of 60 healthy men and 63 healthy women (aged 18-31 years) collected during 12 min of sauna bathing was investigated. Thirty men and 31 women were well trained, 33 women were taking oral, hormonal contraceptives. Sweat was deproteinised by adding an equal volume of 5% sulphosalicylic acid., Results: 1. The comparison of the women taking oral contraceptives with the women not taking oral contraceptives showed no qualitative or significant quantitative differences in the excretion of amino acids in thermal sweat collected from the total body surface. 2. The comparison of the trained women with the untrained women neither revealed qualitative or significant quantitative differences in the excretion of amino acids in thermal sweat collected from the total body surface. 3. As compared to the trained men, untrained men excreted in thermal sweat collected from the total body surface significantly more alanine, arginine, citrulline, cystine, glycine, histidine, isoleucine, leucine, lysine, phenylalanine, serine, threonine, tyrosine, and valine. 4. The sex-specific comparison of the amino acid excretion in sweat showed that men had a significantly increased excretion of cystine, histidine, leucine, and taurine. Proline was detected only in the sweat of women. 5. The quantitative results obtained for the amino acid excretions during 12 min of sauna bathing suggest that persons exposed to hard, physical activity and/or high environmental temperatures have quite equal amino acid losses in sweat and in 24 h urine.