Structure-action relationships

Mclsaac, W., Estevez, V. Structure-action relationship of beta-carbolines as monoamine oxidase inhibitors. Biochem. Pharmacol. 15 1625, 1966. 

It has been recognised for some time (see for example reference 1), that surfactants can increase the rate and extent of transport of solute molecules through biological membranes by fluidisation of the membrane. It is only recently, however, that sufficient work has been carried out to allow some analysis of structure-action relationships. In this overview an attempt is made, by reference to our own work and to work in the literature, to define those structural features in polyoxyethylene alkyl and aryl ethers which give rise to biological activity, especially as it is manifested in interactions with biomembranes and subsequent increase in the transport of drug molecules. 

Bowman WC, Rodger IW, Houston J, et al. Structure action relationships among some desacetoxy analogs of pancuronium and vecuronium in the anesthetized cat. Anesthesiol 1988 69 57-62. 

In the 1920s a most significant change in analgesic research came about the beginning of the first systematic study of structure-action relationships which endeavored to separate analgesic effectiveness from side-effects and addiction liability. 

Ariens, E.J 1966 Receptor Theory and Structure-Action Relationships. Adv Drug Res. 3 235-285 ... 

D. A. Paterson, R. A. Conradi, A. R. HUgers, et al. A nonaqueous partitioning system for predicting the oral absorption potential of peptides. Quantitative Structure-Action Relationships, 13, 4-10 (1994)... 

A set of 4-amino-3-aryltriazoles, each one further substituted by a 5-amide, -ester, or -nitrile group, inhibited these enzymes adenosine deaminase, guanine deaminase, and xanthine oxidase. Structure-action relationships were discussed (79MI1 85FES73). 

The chemical properties and hence the chemical structure of a compound definitely determine its participation in the partial processes making up the various phases of action. The relationship of structure to action is therefore a fundamental characteristic of the action of pharmaca. The apparent absence of such a relationship can only be due to deficient methods of investigation and to the multiplicity and complexity of the processes involved. The structure-action relationship will be found to emerge more clearly if it is studied with regard to particular part-processes such as those involved in pharmacon metabolism, in pharmacon distribution, and in pharmacodynamics. Such a study involves the use of simple, isolated test systems. 

Efforts to detect the structure-action relationship usually emphasize the significance of particular moieties in the pharmacon molecule for particular aspects of its action1,2 49 S1). Chemical modification of the structure of a bioactive compound in efforts to modulate its action in practice always involves changing particular moieties in the molecule1,2>43,49 S1), for instance by substitution52-56. ... 

Fujinami et al. (1976) synthesised fifty-eight N-chloroacetyl-N-phenylglycine esters to study the structure-action relationships in this group of herbicides. 

Schunack, W. (1973) Structure-action relationship of histamine analogs 1. Histamine-like compounds with cyclized side chain. Arch. Pharm. 306 934-942. 

Albert A. The long search for valid structure-action relationships in drugs. J Med Chem 1982 25 1-5. 

Ing HR. The structure-action relationships of the choline group. Science 1949 109 264-266. 

Today, we would say that current insight into structure—action relationships has come principally from a study of physical properties and the receptor theory, and particularly from the reconciliation of these two approaches originally seen as rivals. These two concepts will now be expanded, in turn. 

These studies of structure—action relationships in the aminoacridines established that nucleic acids can be the site of receptors. In fact, the drug-receptor interaction was observed here in unusual detail, much of it at the level of molecular biology (for further details, see Section 10.3). 

This chapter has traced the slow, hesitant steps by which drug workers have advanced beyond the belief that structure—action relationships depended on particular substituents or nuclei, and how they gradually learnt to appreciate the importance of physical properties. At the present time it is considered that three properties are most relevant (i) partition, (ii) ionization (or other... 

After examination of 106 chlorinated cyclodiene insecticides on six selected types of insect. Soloway (1965) concluded that a strict geometry governs ability to react with insect receptors. Two electron-rich sites are required (Cl, O, N, S, or double bond) for electrostatic adsorption (dihydro-aldrin has only one such site, and has only a low toxicity to insects). Aldrin 6.46) is a typical example. Chemically it is efo- wrf(9-l,2,3,4,10,10-hexachloro-l,4 5,8-dimethano-hexa-hydronaphthalene. The critical outline which these nearly spherical molecules require for activity is shown in 6,47), it was produced by viewing molecular models along a line joining the bridgehead (methano) atoms. Lindane, which has a similar mode of action, has a similar outline. For further details of structure—action relationships, see Brooks (1974). 

For further reading on folic acid biochemistry, see Blakley (1969) for a review of structure—action relationships in 2,4-diamino-pyrimidines, -pteridines, and -quinazolines, as anti-bacterial, anti-cancer, or anti-malarial drugs, see Roth and Cheng (1982) and Roth, Bliss and Beddell (1983). 

The basic methodical approach in receptor studies is that of quantitative estimations of the relationship between drug concentration and effect evoked, by quantitative analysis of agonist—antagonist interaction and by studying structure-action relationships. 

The structure-action relationship in -adrenotropic drugs differs strikingly from that in a-adrenotropic drugs although the same regions of the molecule are still of importance (see Table 5). 

Table S. Structure-action Relationships of some /I-adrenotropic Drugs...

Table 7. Structure-action Relationships in some Muscarinomimetic Drugs IN Producing Rat Jejunum Contraction...

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