Some Relationships Between Chemical Structure and Pharmacological Activities

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Abstract
One of the earliest and most general parameters of interest was the ionization characteristics of biologically active molecules. Charge distribution is increasingly being considered. Among some local anesthetics, not only pKa values but infra-red absorption characteristics and charge distribution as well as other properties have been assessed. Correlations are limited to narrow ranges of structural variations. Measuring the influence of pH on activity in a suitable biological test system is another approach to assessing the influence of ionization. Linear free energies and partition characteristics have been associated with biological activities. From so-called substituent constants, effects of groups were factored into electronic, steric, and hydrophobic components makes an interesting case for consideration of molecular orbital calculations in SAR [Structure-Activity Relationships] utilizing some cholinesterase inhibitor models. More attention will be paid to the behavior of [pi] electrons in biochemical phenomena and SAR. The effect of temperature on neuromuscular junction activity of some quaternary ammonium compounds has been interpreted in terms of their physical chemical properties such as ionic characteristics and charge distribution, hydrophobic character and steric features. Lipid solubility has been assumed to account for the penetration of a variety of classes of drugs through membrane barriers, especially with the central nervous system and blood brain barrier. Recent studies include partition coefficient determinations for cholinomimetic and cholinolytic drugs, with centrally active members favoring lipophilic distribution. Ionization constants and partition coefficients of some 2-benzyl-benzimidazole related analgesics were interpreted as possibly influencing transport characteristics and thereby activity, but these factors alone could not account for the properties of all members in that structural specificities also seemed involved. The ability of a number of psychoactive drugs to interact with anionic (phospho) lipid films has been interpreted as evidence that these agents penetrate such films.