Drug molecule properties

An overview of these drug molecule properties allows further consideration of the definition of a pharmacophore provided two paragraphs previously (Wermuth, 2006) ... 

An article entitled When Drug Molecules Look in the Mirror in the June 1996 is sue of the Journal of Chemi ca/fdc/cat/on (pp 481-484) describes numerous exam pies of common drugs in which the two enantiomers have different biological properties... 

The temperature of a simulation depends on your objectives. You might use high temperatures to search for additional conformations of a molecule (see Quenched Dynamics on page 78). Room temperature simulations generally provide dynamic properties of molecules such as proteins, peptides, and small drug molecules. Low temperatures (<250 K) often promote a molecule to a lower energy conformation than you could obtain by geometry optimization alone. 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

Cannabinoids were used in medicine in the form of their crude extracts many centuries ago. Lately the use of cannabis for so-called recreational purposes has become a national vice of substantial proportions. Several attempts have been made to focus the potentially useful pharmacological properties of marijuana into drug molecules with no abuse potential. 

In general, there are three milestones for the drug discovery process. The first is the identification of a verified hit series (primary activity in a related series of molecules), the second the determination of a lead series (series with primary activity and drug-like properties), and the third a clinical candidate (activity, positive pharmaceutical, and pharmacokinetic properties devoid of toxicity). An example... 

Thus, the biological activity of a drug molecule could be expressed as a function of its electronic, hydrophobic, and steric properties, and one or more such factors as hydrogen bonding or polarizability (x) which might be involved. 

Fischer, H., Kansy, M., Bur, D. CAFCA a novel tool for the calculation of amphiphilic properties of charged drug molecules. Chimia 2000, 54, 640-645. 

Such ion-pair constants are conditional , in that they depend on the concentration of the counterion with which the charged drug molecule enters into the octanol phase as an ion-pair. This is due to the low dielectric property of octanol, inducing charge neutrality upon uptake of charged drug molecules. Extraction constants may be used to explicitly include the participahon of the counterion [18]. 

We have discussed now a number of important molecular properties which are used to profile lead and drug molecules. In many cases, certain combinations of these properhes are correlated to some extent within a series of compounds. In particular, the size-related properties of MW, PSA, and log P show this tendency. One should be aware of this phenomenon and it should be taken into account when interpreting the underlying SAR data. However, there is no strong correlation between these three properties in general. When looking at a random subset of 10000 compounds from GVKBIO [9], we find that MW and log P are correlated with r=0.32, log P and PSA with r=0.35, and MW and PSA with r=0.61. 

Dynamic aspects of drugs delivered into lipid bilayer membranes are significant in discussing bioactivities and the mechanism of the drug-membrane interactions. So far, however, the dynamic properties of drugs in the membrane interior have not been well understood. No systematic NMR experiments have been carried out because of the low concentration of the bilayer interior. In this section, we illustrate how to obtain dynamic features of drug molecules trapped in membranes by NMR. 

Using molecular mechanics calculations to assess the three-dimensional shape of a molecule, various surface properties such as polarity and size can be calculated. The dynamic molecular surface properties can be determined from the (low energy) conformation(s) of the drug molecule obtained by molecular mechanics calculations of conformational preferences. The potential advantage of this method is that the calculated surface character-sitics determine numerous physicochemical properties of the molecules including lipophilicity, the energy of hydration and the hydrogen bond formation capacity [187-... 

The next term in Eq. (1) that can be manipulated is Cs, the saturation solubility of the drug. This variable can be influenced by both patient and pharmaceutical variables. The patient variables include the changes in PH as well as the amounts and types of secretions along the GIT. Additionally, both the physical and chemical properties of a drug molecule can be modified to increase or decrease its saturation solubility. 

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