Dual effect groups

Cholesterol can modify both the hydrophobic attraction between lipid hydrocarbon chains and electrostatic interactions between lipid polar groups. The influence it has on the location of 9HP reflects this dual effect At low temperature, the "spacer" effect of cholesterol allows the ketone to gain access directly to the lipid-water interface. At high temperatures, a more disordered hydrocarbon core favors the solubilization of the guest molecule. 

Electron-donating groups have a dual effect rate enhancement owing to electronic factors, as expected for electrophilic aromatic substitution, and a rate deerease as a result of steric and transport restrictions. Even the size of the methyl group in toluene is sufficient to compensate for the increased electron density on the aromatie nucleus, as shown by competition kinetics (benzene/toluene 1 1.3 for TS-I/H2O2, 1 10 for trifluoroperacetic acid) [2,27]. The nuclear reactivity trend of alkylbenzenes was in the sequence toluene > /7-xylene > ethylbenzene > /7-methylethylbenzene, in accordance with increasing molecular size... 

In addition, the conversion of phenols to glycidyl ethers does not follow this ideal pathway, and side reactions or incomplete dehydrochlorination yield compounds containing chlorinated groups such as 12 and 13. These reactions have a dual effect, because they first reduce the number of epoxy groups, which is generally lower than two, and second, they introduce covalently bonded chlorine atoms that can be hydrolyzed under exposure to high temperature and... 

However, in more recent years it has become usual to employ ar or crR-type constants, either together in the dual substituent-parameter equation or individually in special linear regression equations which hold for particular infrared magnitudes. In this connection a long series of papers by Katritzky, Topsom and their colleagues on Infrared intensities as a quantitative measure of intramolecular interactions is of particular importance. We will sample this series of papers, insofar as they help to elucidate the electronic effects of sulfinyl and sulfonyl groups. 

Finasteride has been clinically proved to reduce the median volume of the prostate in patients and is currently prescribed for the treatment of BPH. The compound also has demonstrated efficacy in the treatment of male pattern baldness and is prescribed for this indication as well. Subsequent to the discovery of finasteride, it was found that there are two isoforms of steroid 5a-reductase in mammals, type 1 and type 2. The type 2 isoform is primarily active in reproductive tissue, while the type 1 isoform contributes to DHT formation in the skin, liver, and reproductive tissue. Finasteride inhibits both isozymes in rats, but selectively inhibits the type 2 isozyme only in humans. It is hypothesized that dual inhibition of both isoforms of steroid 5a-reductase might prove more effective in treating BPH. Hence the GlaxoSmithKline group identified and developed dutasteride (Figure 8.18C). Dutasteride inactivates both human isoforms of steroid 5a-reductase by a mechanism similar to that described for finasteride (Bramson et al., 1997 see also the Web site www.avodart.com). Both finasteride and dutasteride have demonstrated clinical efficacy and are currently used in the treatment of BPH. 

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