Micellar chromatographic determination of partition coefficients and associated thermodynamic data for pharmaceutical compounds

Micelle/water partition coefficients were obtained for procaine hydrochloride using micellar liquid chromatography (MLC) to illustrate the potential application of this technique to compounds of pharmaceutical interest. Experiments were conducted over a temperature range which led to calculation of a Gibbs free energy, enthalpy and entropy of transfer for procaine hydrochloride. Successful application of this technique was confirmed using a second compound over a range of temperatures, namely caffeine. Overall, this work confirms that MLC can be used to determine precise and accurate partition coefficients that possibly more closely mimic biological membranes than traditional in vitro systems, namely octanol/water.     

A chemoenzymatic approach to (+)-pilocarpine

A short synthesis for the alkaloid (+)-pilocarpine has been developed. Key step of this synthesis is a chemoenzymatic resolution utilizing the lipase AP.     

A Study of the Lipophilicity of Amide Derivatives of α-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-γ-hydroxybutyric Acid by Use of RP-TLC and Calculation

JPC – Journal of Planar Chromatography – Modern TLC - Evaluation of the lipophilicity of derivatives of N-benzylamides and N-phenylethylamides of...     

Opioid peptides: synthesis and biological properties of [(N gamma-glucosyl,N gamma-methoxy)-alpha, gamma-diamino-(S)-butanoyl]4-deltorphin-1-neoglycopeptide and related analogues

The [D-Ala2]deltorphin 1 sequence in which the aspartic acid residue is replaced by the N gamma-OCH3-alpha, gamma-diamino (S) butanoyl residue was synthesized using the Fmoc-chemistry-based solid phase procedure. The resulting deltorphin analogue was chemoselectively glucosylated by reaction with unprotected D-glucose (Glc). The Asn4-, (2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-galactopyranosyl)-Asn4- and the (2-acetamido-2-deoxy-D-galactopyranosyl)-Asn4-deltorphin I were also prepared for comparison. The affinity of the new compounds for the delta-opioid receptor was expressed by the inhibition constant (Ki) of the binding of the delta-receptor selective ligand [3H]naltrindole (NTI) to rat brain membrane preparations. The in vitro biological activity of the synthetic peptides was compared with that of the mu-opioid receptor agonist dermorphin in guinea pig ileum (GPI) preparations and with that of the delta-opioid receptor agonist deltorphin I in mouse vas deferens (MVD) preparations. The substitution of Asp4 with Asn failed to affect drastically the Ki and IC50 values for delta-sites, suggesting that an electrostatic interaction does not play an essential role in the binding to delta-opioid sites. The steric hindrance of the side chain of the residue in position 4 affects binding to delta-sites. The increase of the Ki value is smaller when the sugar-peptide linkage involves the gamma-nitrogen of the Dab residue in comparison with the Asn amide side chain.