It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.

/pdf/fluorine-in-medicinal-chemistry-4kwoqx8yba.pdf

Fluorine in medicinal chemistry.

Since its first use in the steroid field in the late 1950s, the use of fluorine in medicinal chemistry has become commonplace, with the small electronegative fluorine atom being a key part of the medicinal chemist's repertoire of substitutions used to modulate all aspects of molecular properties including potency, physical chemistry and pharmacokinetics. This review will highlight the special nature of fluorine, drawing from a survey of marketed fluorinated pharmaceuticals and the medicinal chemistry literature, to illustrate key concepts exploited by medicinal chemists in their attempts to optimize drug molecules. Some of the potential pitfalls in the use of fluorine will also be highlighted.

18-hydroxycorticosterone: a review.

Publisher Summary A critical analysis of the action of histamine (H) on the central nervous system must consider the route of administration (intravascular, intraventricular, or intracerebral ), the visceral, somatic behavioral, and electrographic effects of this substance on the central nervous system. The neurophysiological approach is rather recent and particularly important, since the neurohumoral nature of H becomes more and more evident. Scarcely investigated was histamine's involvement in the regulation of wakefulness and its relations to other neurohumors, such as catecholamines or serotonin. Previous experimental data suggested that H has a definite waking effect, but the mechanisms of this effect need closer analysis. This chapter reviews, on one hand, the previous investigations devoted to the action of H on the central nervous system. On the other hand, it reports the results of the experiments performed to differentiate the mechanisms of the agerent and central effects of H on the brain. It is indeed necessary to specify the extent to which the waking effect is mediated reflexly by afferent systems and the extent to which it is of a direct central nature.

The activating effect of histamine on the central nervous system.

M. Palem-Vliers

Papers

Molecular configuration and conformation of aldosterone, 18-hydroxy-11-deoxycorticosterone and a new urinary 18-hydroxy-steroid--an N.M.R. study.

Structure-activity relationships for agonistic and antagonistic mineralocorticoids

Physico-chemical characterization of cytosol and nuclear mineralocorticoid receptors in rat kidney

Role of hydrophobic effects and polar groups in steroid-mineralocorticoid receptor interactions.

Effect of 6-dehydro-doca and 6-dehydro-9αfluorocortisol acetate on the excretion of sodium and potassium in the rat