Lipophilic Character of Pyrimidinic Nucleoside Derivatives: Correlation Between Shake Flask, Chromatographic (Rp-TLC and Rp-Hplc) and Theoretical Methods

Abstract

Chromatographic R Mw and log k' w parameters have been used as alternatives to the shake flask n-octanol/water partition coefficient method to study the lipophilic character of several known pyrimidinic nucleoside derivatives and two novel ones. The R M and log k' values were measured by means of reversed-phase thinlayer chromatography (RP-TLC) and reversed-phase high performance liquid chromatography (RP-HPLC) respectively. Good linear relationships were observed between log P values obtained from the classical shake flask method (log P o/w ) and each one of those obtained by chromatographic techniques (log P RP-TLC and log P RP-HPLC ) and by theoretical calculations using the CLOGP program (log P CLOGP ). The R Mw and log k' w values have proven to be reliable parameters for describing the lipophilic properties of this family of compounds. 855

Human Serum Albumin Binding of Novel Antiretroviral Nucleoside Derivatives of AZT

“…These compounds exhibit anti-HIV and in vitro bactericidal activities as well as relevant physicochemical properties in the medicinal chemistry area (13)(14)(15)(16)(17).…”

Lipophilic Character of Novel Amino Acid Derivatives of Zidovudine With Anti Hiv Activity

“…The procedure was feasible because a thermodynamic marker (KI) was used to determine the solvent front in the R M determination. [20,21] Relationship Between R Mw and log P o=w…”

“…Based on the high stability over a wide range of mobile phases observed in a previous work, [20] RP-18 HPTLC F 254S , 5610 cm precoated TLC plates, purchased from Merck (Darmstadt, Germany) were used for the determination of the chromatographic hydrophobic constant. Drugs 1, 2a, 3-8 were dissolved in an appropriate volume of methanol, in which they appeared to be stable to hydrolysis, reaching a final concentration of 1 mg=mL.…”

“…In order to determine the thermodynamically true solvent front position, [20,21] a solution of potassium iodide was used as marker, and was prepared by dissolving 50 mg of drug in 10 mL of a water-ethanol mixture (25 : 75, v=v). A 50 mL aliquot of the marker solution was spotted onto the plate in several positions to determine the thermodynamically true solvent front line.…”

“…The n-octanol-buffer, pH 2, partition coefficients of 3-8 were measured by means of the shake flask method, [4] applying the equations previously reported: [20] P…”