PALLAS for WINDOWS


Software predicting pKa,logP, logD values and metabolites based on structural formulae of compounds

Introduction

In the field of industrial pharmacy perhaps the most important physicochemical characteristics of drugs and excipients are their acidity or basicity (expressed by their pKa value), their hydrophobicity and it's dependence on pH (expressed by their logP and logD values respectively). Whether in research and development or in drug quality control, these values can be used in a variety of situations.
To determine precision values of pKa, logP or logD presents a great deal of work. Thus the use of computers is giving great progress to the practice.
The profile in reaction kinetics depends closely on pKa values (1,2,3). In preparative chemistry, pKa values of the reaction products can be used to select conditions for synthesis. The knowledge of the pKa values of intermediate products is also important, although they are often very difficult to measure. In many cases the chemist can save much time and cost using predicted pKa values.

Frame - This module is the frame of PALLAS which is a collection of powerful tools for making predictions based on the structural formulae of compounds. It has a modular structure allowing to attach each prediction module separately to the system. It allows you to maintain and predict large databases of compounds.
You can enter the compound structure graphically, import it from different file-formats. The results can be printed out in a high quality format or exported to any spread-sheet editor.

pKalc 3.1 predicts the pKa values of organic compounds. The prediction is based on the structural formulas of the compounds. The pKa values of the compounds are predicted using approximately 300 Hammett and Taft equations, which were partly taken from the collection of Perrin et al.(4) with the rest were developed by CompuDrug.
We have compared predicted pKa values of about 400 drugs with measured values.

The logP value is the logarithm of the partition coefficient of the compound in organic phase/water systems. Nowadays, the most widely used organic phase in logP determinations is octanol. It has been known for a long time, that the biological activity of a drug is related to it's logP (5,6). This is because the absorption of a compound depends on its partition between the biological membrane and the aqueous phase. LogP values are also important in separation technics and the prediction of the solubility of drugs. There are many methods to measure logP, but in several cases, when only an approximate value is needed, a logP prediction can adequately substitute it.

The PrologP 5.1 computer program predicts the logP values based on the structural formulas of the compounds. The program uses three different systems for the prediction. These systems disintegrate the compound to fragments, and express the logP value as a superposition of the corresponding fragment constants (7,8). The latest superposition method uses about 150 atomic fragments (9).

Contrary to logP, in which only one species (usually the neutral one) of a compound is accounted for, logD expresses the hydrophobicity of the compound at a given pH, considering all species of the compound. The logD value (the logarithm of the apparent partition coefficient) is the ratio of the sums of the concentration of all forms of the compound in octanol and water. The concentration of the ionized forms in the organic phase is much less than that of the neutral form.

PrologD 2.0 can predict the logD values of the compounds. It is based on the pKa and logP prediction of the neutral form and on the calculation of the micro and macro dissociation constants of the compound. The input of the program is the structure of the compound and the Na+, K+ and Cl- concentrations of the aqueous phase.

MetabolExpert 10.0 An expert advisory system for the prediction of the metabolism of exogenous compounds in plants and mammals. It operates based on a comprehensive knowledge base which consists of two transformation databases of reaction rules (one for plants and the other for animals).

Try out our demo version of PALLAS. Using this demo you can try all features of the program. Note that you cannot predict compounds other than those included in this demo.
Demo version of PALLAS is freely distributed.

UNIX versions - All prediction modules can be run in command line mode or via Xpred 1.0

Dos software

Price list for North America, Europe and elsewhere other than North America or Japan.


If you have more questions send a message !
References:

  1. A.J.Kresge,Chemtech, April, 250 (1986)
  2. Francois Terrier, Hai-Qi Xie, and Patrick G. Farrell, J.Org.Chem., 55, 2610 (1990)
  3. J.P.Guthrie, and J.Cossar, Can.J.Chem., 64, 2470 (1986)
  4. Perrin D.D.,Dissociation constants of organic bases in aqueous solution, supplement 1972,Butterworths,London
  5. C.Hansch, R.M.Muir, T.Fujita, P.P.Maloney, F.Geiger and M.Streich, J. Am. Chem. Soc., 86, 1616-1626 (1964)
  6. H.Kubinyi, J. Med. Chem., 20, 625-629 (1977)
  7. P.Broto, G.Moreau, C.Vandycke, Eur. J. Med. Chem. - Chim. Ter., 19, 71 (1984)
  8. A.K.Ghose, G.M.Crippen, J. Computat. Chem., 7, 565 (1986)
  9. V.N.Viswanadhn, A.K.Ghose, G.R.Revankar and R.K.Robins, J. Chem. Inf. Comput. Sci., 29, 163-172 (1989)
Zoltan Deak:
zdeak@eik.bme.hu