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In the present paper two theophylline esters with poly (ethylene glycol) (PEG) and methoxy poly (ethylene glycol) (mPEG) were prepared. Quantitative yields of the pure products were obtained. Unlike the free drug, the drug-polymer conjugates are freely water-soluble at room temperature. In vitro release experiments in aqueous buffer demonstrate that both conjugates are stable in buffer of pH 7.4 and 1.2. In vivo release studies after oral administration of theophylline conjugates demonstrate a good release of parent drug.

Two known antiherpetic agents, acyclovir and valaciclovir, were coupled with activated poly(ethylene glycol). In vitro drug release studies demonstrated the conjugates to be stable in buffer solutions at pH 7.4 and 5.5, while only PEG-valacyclovir2 was stable in a buffer solution at pH 1.2. The ability of the macromolecular conjugate to release the free drug was also evaluated in plasma, in which the most stable prodrug also proved to be PEG-valacyclovir2. The derivatives are degraded in the presence of proteolytic enzyme. The rate of hydrolysis was monitored by HPLC-analysis.

The two pairs of enantiomers of isoxazolidin-3-ones 3 and 4 were synthesized by means of Lipase PS-catalyzed hydrolyses of suitable racemic butyrates. The same butyrates were also employed as key intermediates in the preparation of racemic 3 and 4. The antimuscarinic potency of the new compounds was assayed in two in vitro functional tests. The eutomers (-)-3 and (-)-4 share the same stereochemistry (5R) of the most potent enantiomer of "azamuscarone" 2, a structurally related muscarinic agonist. Such a spatial arrangement around the chiral center of 2-4, coupled with the low values of eudismic ratio, represents an anomaly among the chiral muscarinic ligands. This anomaly was accounted for by the absence of a chiral center at C-2, a position whose configuration is crucial in determining the high enantioselectivity of muscarinic agonists and antagonists.

The synthesis of 2-(4-amino-5-chloro-2-methoxybenzamido)acetic acid 2, a metabolite of metoclopramide 1, has been accomplished through the coupling of 4-amino-5-chloro-2-methoxybenzoic acid 4 with glycine benzyl ester followed by a catalytic hydrogenation. Such a metabolite could not be detected directly in the human urines but only after its transformation into the corresponding methyl ester 6. Compound 6 was prepared both by condensing acid 4 with glycine methyl ester and by reacting acid 2 with diazomethane. HPLC analyses of biological samples were therefore performed after treatment with diazomethane. In five healthy volunteers, the percentage of 6 spanned the range 0.6-1.2%.

Many assay procedures have been devised to measure lipolytic activity, but none is without problems. It is for this reason that new methods are still being proposed. In this work we have investigated the use of two esters of p-nitrophenol, the palmitic acid and lauric acid esters, as substrates for a highly sensitive high-performance liquid chromatographic method. Data on recovery, specific activity and reproducibility are reported only for the lauric ester, because the palmitic ester turned out to be a very poor substrate.