Effect of fluorine substitution

Table 10 Effects of fluorine substitution on GABAa binding and efficacy...

B.K. Park, N.R. Kitteringham, Effects of fluorine substitution on drug metabolism Pharmaceutical and toxicological implications, Drug Metab. Rev. 26 (1994) 605-643. 

Effects of fluorine substitution on inhibition of SSAO by cyclopropyl amines 683... 

In Section 1.3, the general effects of fluorine substitution on drug activity and selectivity have been treated. As seen frequently with other enzymatic reactions, introduction of fluorine can have dramatic effects on the properties of substrates and inhibitors of MAOs [26]. For example, preliminary studies indicated that fluorination of 5-hydroxytryptamine in the 6- or the 4,6-positions (3,4) causes this predominantly MAO A substrate to be metabolized significantly by platelet MAO B [27]. Although no direct evidence was obtained, this may be caused by increased lipophilicity introduced by fluorine substitution. 

As previously discussed, L-deprenyl (2) is a selective suicide inhibitor of MAO B. As part of a program to develop [ F]-labeled L-deprenyl for PET studies, Fowler and coworkers prepared [ C]-labeled o- and L-4-fluorodeprenyl (37) to study the effects of fluorine substitution on kinetics of uptake and localization [105]. Subsequently, no-carrier-added o,L-4-[ F]-fluoroderprenyl (38) was made by a nucleophilic aromatic substitution reaction [106],... 

As discussed above, many cyclopropylamines are good inhibitors of MAOs. In addition, as discussed in Section 3.2, fluorine substitution had substantial effects on the inhibition of MAOs by such analogues as allylamines. We undertook a broadly based study of the effects of fluorine substituted on the cyclopropyl ring of cyclopropyl amines on potency and selectivity of amine oxidase inhibition. In addition to effects on amine pKg and lipophilicity, we expected additional consequences resulting from altered geometry and ring strain due to the presence of fluorine. 

With respect to the effects of fluorine substitution on the behavior of cyclopropy-lamines as MAQ inhibitors, the results of the work of Fuller and Molloy with... 

Enzyme inhibitors can be designed through different ways taking into account the effects of fluorine substitution on the behavior of a substrate toward the enzyme. Many fluorinated inhibitors (reversible or irreversible) have been studied. In this chapter, we only consider cases in which fluorine atoms play a determinant role in the inhibition and which are of importance in dmg discovery. We successively focus on the following ... 

Effect of Fluorine Substitution on the anti-HIV Activity of Dideoxynucleosides ... 

Studies on the organo-transition metal chemistry of OFCOT and other fluorocarbons indicate that organometallic molecules with perfluorinated carbon skeletons possess structural and chemical properties equally as rich as their hydrocarbon analogues. Their structures and chemistry have helped our understanding of the effects of fluorine substitution on the physical and chemical behavior of organometallic compounds. 

Because of the rate-enhancing effects of fluorine substitution on cyclization reactions of partially-fluorinated radical systems, it is likely that, unlike for pure hydrocarbon systems, it will be possible to utilize such processes to make six-, seven-, and even larger membered rings in radical systems which have appropriate fluorine substitution. 

Baker, J. M. Dolbier, W. R. Density functional theory calculations of the effect of fluorine substitution on the cyclobutylcarbinyl to 4-pentenyl radical rearrangement. J. Org. 

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