Structure Action

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

Sometimes we ve come across a team busily engaged in writing a thick document that contains miles and miles of formally structured action specs. This is a write-only document, and it is likely to be a work of fiction by the time it is finished. Formal notation (pictures and formal text) is good at being unambiguous pictures, in particular, are good at explaining complex relationships that would be difficult to get hold of in ordinary narrative. 

Figure 5.2). Panels can be quite strong since this is a very efficient structural action however, end anchorage is extremely important to achieving significant capacity. Resistance to blast loads of more than 2-4 psi (14-28 kPa) will normally require tensile membrane response. 

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. 

The first synthetic zeolites were known as Linde Molecular Sieves but are now marketed as Union Carbide Molecular Sieves they are available from Union Carbide International Company, USA. or Union Carbide (UK) Ltd directly, or through the usual chemical suppliers, t Booklets giving detailed information on the structure, action and applications of molecular sieves are available from most suppliers of laboratory chemicals. 

Computer modelling has reduced the need to synthesize every analogue of a lead compound. It is also often used retrospectively to confirm the information derived from other sources. Combinatorial chemistry, which originated in the field of peptide chemistry, has now been expanded to cover other areas. The term covers a group of related techniques for the simultaneous production of large numbers of compounds for biological testing. Consequently, it is used for structure action studies and to discover new lead compounds. The procedures may be automated. 

The serotonergic system is involved in a large number of physiological functions, resulting from its widespread innervation of the brain. The axons of serotonergic neurons of the midbrain raphe nuclei reach almost every brain structure. Action potentials traveling along these axons release 5-hydroxytryptamine... 

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. ... 

The structure-action investigation of N-cyclohexyl-2-methyI-3-furamides resulted in the discovery of a new active substance (Pommer and Zeeh, 1977). 

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. 

The strategies for the improvement of organie meat distribution rely mainly upon putting into practice structural actions within the ehain aimed at increasing the supply. Also, channel diversification and promotional actions are considered useful in order to ease the advance of the organic meat chain. This implies that operators perceive the need to increase their bargaining power, which currently appears still rather low. 

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). 

Because good anti-depressive and good neuroleptic activity is found in substances with a nucleus of three fused rings, but the two properties never occur in the one compound, an exploration was made of structure—action relations in the two systems (Wilhelm and Kuhn, 1970). The topology of the tricyclic skeleton determines the type of activity, but this is modified by the side-chain. 

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