Separation, analyses and syntheses of trimethoprim impurities.

The analysis of several impurities of the chemotherapeutic agent trimethoprim with various methods, including thin layer chromatography, gas chromatography, capillary electrophoresis as well as nuclear magnetic resonance is described. These methods were used to identify new impurities in trimethoprim batches. The main impurities were separated by column chromatography.

[PAF-antagonists with lipid structure. 6. Alkylpropandiol lipids with acyl- and ether- structures at the C-3 position and heterocyclic head groups; synthesis, characterization and structure-activity relationship].

A series of 14 PAF-analogues with simple lipid structure and heterocyclic head groups were synthesized, and the PAF-inhibitory potencies on human blood platelets was evaluated in vitro. Structure-activity relationships revealed that the PAF-antagonist activity is strongly influenced by the distance between position C-3 of the backbone and onium center and the structure of the heterocyclus. The best activity showed the 3,5-dimethylpyridinium derivative with a distance of 5 methylene groups (IC50 = 0.

[PAF-antagonists with a phospholipid structure. 5. Propanediol phospholipids with various substituted pyridinium and quinuclidinium head groups and variations of the phosphorus-nitrogen distance;synthesis, characterization and structure activity relationship].

A series of 10 PAF-analogues, structurally modified in position C-2 (n-propyl) and position C-3 (polar head group) were synthesized, and the PAF-inhibitory potencies was evaluated using PAF-induced aggregation of human blood platelets in vitro. Structure-activity relationships revealed, that the PAF-inhibitory activity is strongly influenced by the distance between phosphate and onium center and the structure of the substituted heterocyclus. The best activity was observed by 3,5-dimethylpyridinium- and 4-ethylpyridinium derivative with a P-N-distance of 6 methylene groups (IC50 = 1.

[PAF-antagonists with phospholipid structure. 4. Alkylcarbamoylphospholipids with heteroarene and heterocyclase head groups and variation of the P-N-distance; synthesis, characterization and structure-activity relationship].

A series of 11 PAF-analogues, structurally modified in position 1 (alkylcarbamoyloxy), position 2 (n-propyl), and position 3 (polar head group) were synthesized, and the inhibitory potencies on human blood platelets in vitro was evaluated. Investigations of structure-activity relationships revealed, that the PAF antagonist activity is strongly influenced by the chain length of the alkylcarbamoyl residue and the structure of the polar head group. Derivatives with pentadecyl and octadecylcarbamoyl structure emerged effective inhibitors.

Synthesis and proaggregatory activity of 1-O-(2-methyloctadecyl)-2-O-acetyl-rac-glycero-3-phosphocholine.

Racemic 1-O-(2-methyloctadecyl)-2-O-acetyl-glycero-3-phosphocholine, a branched chain PAF species, was prepared by chemical synthesis and investigated for biological activity on human blood platelets in vitro. The synthesis started from 2-O-benzylglycerol and 2-methyloctadecyl-1-methyl sulfonate and was accomplished in five reaction steps. A comparison with 'octadecyl-rich' PAF showed that the PAF species described here exerts a 22-fold weaker proaggregatory activity.