Physiological Action and Chemical Constitution

RsPbX type have the highly disagreeable physiological property of being active sternutators. However, marked alterations in pharmacological action can be effected by variations in structure. 

In connection with the introduction of water-solubilizing groups we found that this could be realized effectively by formation of onium derivatives. As an illustration of another approach, triphenyl-y-diethylamino-propyllead (formed in 91% yield from Ph3PbLi and y-diethylaminopropyl chloride) gave by customary procedures the quaternary ammonium sulfate. 

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Relationship between physiological action and chemical constitution in the fluoroacetate series 133... 

Relationship between Physiological Action and Chemical Constitution in the Fluoroacetate Series1... 

The connections between chemical constitution, on the one hand, and colour or physiological action on the other have been continually studied for many years, but the allied property of odour has only engaged occasional attention within quite recent times. 

Crum Brown A, Frazer TR. On the connection between chemical constitution and physiological action. Part I. On the physiological action of the salts of the ammonium bases, derived from strychnia, brucia, thebaia, codeia, morphia, and nicoti. Trans R Soc Edinburgh 1869 25 151-203. 

In 1868 two Scottish scientists, Crum Brown and Fraser [4] recognized that a relation exists between the physiological action of a substance and its chemical composition and constitution. That recognition was in effect the birth of the science that has come to be known as quantitative structure-activity relationship (QSAR) studies a QSAR is a mathematical equation that relates a biological or other property to structural and/or physicochemical properties of a series of (usually) related compounds. Shortly afterwards, Richardson [5] showed that the narcotic effect of primary aliphatic alcohols varied with their molecular weight, and in 1893 Richet [6] observed that the toxicities of a variety of simple polar chemicals such as alcohols, ethers, and ketones were inversely correlated with their aqueous solubilities. Probably the best known of the very early work in the field was that of Overton [7] and Meyer [8], who found that the narcotic effect of simple chemicals increased with their oil-water partition coefficient and postulated that this reflected the partitioning of a chemical between the aqueous exobiophase and a lipophilic receptor. This, as it turned out, was most prescient, for about 70% of published QSARs contain a term relating to partition coefficient [9]. 

The perception of flavor is a fine balance between the sensory input of both desirable and undesirable flavors. It involves a complex series of biochemical and physiological reactions that occur at the cellular and subcellular level (see Chapters 1-3). Final sensory perception or response to the food is regulated by the action and interaction of flavor compounds and their products on two neur networks, the olfactory and gustatory systems or the smell and taste systems, respectively (Figure 1). The major food flavor components involved in the initiation and transduction of the flavor response are the food s lipids, carbohydrates, and proteins, as well as their reaction products. Since proteins and peptides of meat constitute the major chemical components of muscle foods, they will be the major focus of discussion in this chapter. 

Occurrence, Extraction and Purification—The Allotropy of Selenium—Colloidal Selenium—General Physical Properties of Selenium—Chemical Properties— Applications of Element—Physiological Action—Atomic Woighl—Valency— Constitution of Selenium Molecule—Detection and Estimation of Selenium. 

Easson, L. H., Stedman, E., Studies on the relationship between chemical constitution and physiological action. V. Molecular dissymmetry and physiological activity. Biochem. J. 1933, 27, 1257-1266. 

The effect of ionization on the pharmacological action of drugs was also recognized in the latter half of the nineteenth century. In Scotland, Crum Brown and Fraser demonstrated that quarternization (i.e., the addition of a fourth alkyl group) of several alkaloids resulted in their transition from muscle contractors to muscle relaxants. These researchers concluded that a relation exists between the physiological action of a substance and its chemical composition and constitution, understanding by the latter term the mutual relations of the atoms in the substance. ... 

The goals of QSAR studies were first proposed about 186.5 to 1870 by Crum-Brown and Fraser, who showed that thc grudual chemical modification in the molecular structure of a scries of poisons produced some important differences in their action, They postulated that the physiological action, , of a molecule is a function of its chemical constitution. C. This con be expressed in Equation 2-15 ... 

The concept of specific receptors and sites of drug action has many origins. However, the work of Thomas Fraser and Alexander Crum Brown of Edinburgh University described in their publication of 1869, "On The Connection Between Chemical Constitution and Physiological Action", provides both a definition of structure-activity relationships and a pioneering example of chemist-pharmacologist collaboration (13). 

Fraser T, Crum Brown A. On The connection Between Chemical Constitution and Physiological Action. Neille and Co. Edinburgh, 1869. 

Crum-Brown and Fraser (1868-1869) [Crum-Brown, 1864,1867 Cmm-Brownand Fraser, 1868] proposed the existence of a correlation between biological activity of different alkaloids and their molecular constitution. More specifically, the physiological action of a substance in a certain biological system (4>) was defined as a function (/) of its chemical constitution (C) ... 

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