The molecular properties of the active substance have an impact on their pharmacokinetics and bioavailability. To simplify prove of bioequivalence of generics with reference to medicinal products various exemption procedures and rules were implemented. One of them is substitution of in vivo bioequivalence study by in vitro dissolution similarity determination. This makes a base for so called Biophamaceutical Classification System (BCS). The main two properties are considered: solubility and permeability. Experimental determination of those parameters is cumbersome and frequently impossible. Therefore theoretically derived determinants are promising tool for fast chemical substance classification within BCS. The water solubility determination can be efficiently made based on free enthalpy of solvation (∆G), while permeability can be described by the hydrophobic properties in a first approximation. The hydrophobic properties can be established based on solvation energy in solvent with different polarity. In this study we focused on the important from therapeutic view-point antimycotic medicinal products containing the imidazole ring. Here we calculated ∆G of solvation by water and chloroform molecules at the Hartree-Fock 6-31G* level using SCI-PCM model. For tioconazole and –OH, -CH₂OH and ring derivatives and hydrochloride the values of ∆G of solvation  by water molecules appeared discriminative. The values are as follows: tioconazole ∆G = -0.51 kcal/mol, -OH in 4 position of imidazole ring ∆G = -3.25 kcal/mol, -CH₂OH in 4 position of imidazole ring ∆G = -1.58 kcal/mol, hydrochloride  ∆G = -44.17 kcal/mol. In chloroform, solvent in dielectric constants similar to an octanol the respective values of ∆G are: -5.25 kcal/mol, -2.72 kcal/mol, -3.32 kcal/mol and  -27.17 kcal/mol. Analyzed structural changes give hints to synthesis of compounds with better pharmacokinetic properties of antimycotic agents, the OH substituent appeared to be promising way of parent structure modification.  

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/14722 must be provided.

1. Fullerenes as the carriers of compounds with amide bond
2. Molecular properties of antifungal agents – Impact on bioavailability – The Biopharmaceutics Classification System
3. On tautomerism of the pyridodiazepines. A DFT study.
4. Application of amylose tris(3,5dimethylphenyl- carbamate) chiral stationary phase for the determination of paroxetine, clinically used psychotropic drug
5. Application of silica-bonded ovomucoin protein chiral stationary phase for the determination of paroxetine, clinically used psychotropic drug
6. Examination of optical isomerism - compounds of antihypertensive effects.
7. Molecular properties of active ingredients Impact on bioavailability The biopharmaceutics classification system
8. Direct enantiomeric resolution of tamsulosin, clinically used chiral O-phenylethanolamine derivative with α₁-blocking activity
9. Application of carbohydrate based chiral stationary phase for resolution of  fenoterol, clinically used chiral drug
10. Cyclohexaglycine as a potential ionophore
11. Molecular properties impact on bioavailability of imidazole antifungal agents.
12. Alkyl-nitroquipazine derivatives as serotonin transporter and 5-HT_1A receptor ligands
13. Determination of the enantiomeric purity of epinephrine in pharmaceutical preparations
14. Determination of the enantiomeric purity of norepinephrine in pharmaceutical preparations
15. Comparison of properties of cyclic and linear glycine derived structures and their phosphorus analogues - theoretical studies
16. The ligand binding to the serotonin transporter
17. MOLECULAR PROPERTIES OF SULCONAZOLE AND ECONAZOLE RELEVANT TO BIOAVAILABILITY
18. MOLECULAR DETERMINANTS FOR METABOLIC STABILITY OF NICOTINIC AND PICOLINIC ACID DERIVATIVES
19. DETERMINATION OF SELECTED MEDICINES REDUCING THE LEVEL OF CHOLESTEROL BY CHROMATOGRAPHIC METHODS.
20. IDENTIFICATION AND DETERMINATION OF ANGIOTENSIN II RECEPTOR ANTAGONISTS WITH DENSITOMETRIC METHOD