Lipophilicity, increasing

In Figure 6.5, the count of the number of solute cells diffusing from the W2 compartment, into the membrane, and the number diffusing through the membrane into the Wj compartment is shown for several values of solute lipophilicity. The permeation of solute through the membrane increases with increasing lipophilicity up to about T b(WS) = 0.50, and then decreases as the lipophilicity increases. The concentration of solute within the membrane is very low, as the / b(WS) value increases from 0.15 to 0.45. At a value of Pb(WS) = 0.50, the count of solute molecules in the membrane exhibits a sharp increase at Pb(WS) = 0.55, as shown in Figure 6.5 [5]. 

Lipid solubility. For nonionizable compounds, as the lipophilicity increases, the drug permeability typically increases. To maximize the absorption rate, a drug should be available in the salivary film at its solubility limit. 

Structural features such as electrical charge, hydroxyl groups in the side-chains and amino atoms of the amide groups reduce the lipophilicity (increase the hydrophilicity) whereas additional methyl groups sitting on amino moieties or free positions on the benzene ring increase the fipophilicity. Biliary contrast agents with a free position have > 5. 

Fig. 1 Schematic representation of the separation principle of MEKC. An EOF/ micelle marker and three solutes differing in lipophilicity in the presence of anionic micelles in the background buffer are present. The lipophilicity increases in the sequence Sj < S2 < S3 t—migration time of EOF (nonionic solutes) S (solute) me —micelle.

Conclusions Increase in lipophilicity - increase in potency Increase in pKa -decrease in toxicity... 

In the course of our investigations with the phenylalkylamine 5-HT2 agonists (Section 2.1), we investigated the structure-affinity relationship (SAFIR) for binding. Although the 2,5-dimethoxy pattern was not essential for the binding of these compounds at 5-HT2 receptors, it appeared to be optimal. It was also found that lipophilic substituents at the ring 4-position played a major role in affinity modulation and that affinity increased as lipophilicity increased. For... 

Lipophilicity. In general, the replacement of hydrogen by fluorine in a molecule increases its lipophilicity, particularly with groups such as CF3 and OCF3. Lipophilicity plays a key role in the transport of molecules through plant and insect cuticles. In addition to lipophilicity, increasing the number of fluorine atoms in a... 

As might be expected, the lipophilicity increases with increasing chain length of the carboxylato ligands alkyl group. This increases the body burden of rhodium, which in turn increases both the toxicity and antitumor activity of the rhodium complex. However, it has been stated that too great an increase in the chain length (i.e. beyond the pentanoate) reduces the therapeutic properties.24 It seems that optimal properties are shown by the butyrate.25,26... 

The levels of circulating drug that are achieved are a function of dose, absorption efficiency, overall bioavailability, distribution, and also clearance. The major determinant of drug distribution volume is its lipo-philicity. As lipophilicity increases, so does the ability of the drug to cross biological membranes and move into extravascular environments, particularly into fatty tissue and the central nervous system (CNS). 

The influence of log P of beta-blockers (Table 9.12) on their permeation coefficients into conjunctiva and cornea is shown in Fig. 9.37. In humans, the conjunctiva has 17 times the surface area of the cornea and therefore it absorbs significant amounts of dmg. Work has centred on increasing corneal permeability or retention of the dmg (or product) in the conjunctiva sac. Appropriate doses of dmg can achieve a degree of comeal or conjunctival selectivity, represented in Fig. 9.37(c) by the ratio (C/y). Increasing lipophilicity increases the C// ratio from <0.1 to approximately 0.5. 

Diamorphine (or heroin) is the diacetyl derivative of morphine and, like morphine, is used as a narcotic analgesic (Figure 8.21). The two acetyl groups are important for two reasons first, they render the molecule more lipophilic (increasing the partition coefficient), which means that diamorphine is absorbed into the central nervous system more rapidly than is morphine, and in turn results in a faster onset of action than for morphine (and, sadly, makes the compound a favourite with addicts). The second aspect of the two acetyl groups is that they are susceptible to hydrolysis, to yield morphine and two molecules of acetic acid (Figure 8.21). 

The efficiency of strong acid catalysts for the production of alkyl glucosides products increases as their hydrophobicity or lipophilicity increases. For example, on an equimolar basis, dodecylbenzenesulfonic acid is a more efficient catalyst than para-toluenesulfonic acid in that it produces a higher yield of alkyl glucosides with fewer by-products. 

Table Reasons for lipophilicity increases in discovery projects.

LLEat values show no size dependency. This shows that despite increase in size, the specific interactions between compound and receptor are still utilized effectively. The slight increase in LLE with increasing potency indicates that potency improvements are not brought about by the increase in clogP. In other words, there was no strong correlation between potency and lipophilicity increase (leading edge [49]). LE and FQ values confirm that potency contribution per atom remained constant with increase in size. Since most of the compounds showed no effect in the counterscreen, this cluster was considered for expansion. 

Vegetable oils (such as rapeseed, soybean and palm oils) or animal fats (beef tallow) are used for the production of so-called biodiesel, which is typically made by alcoholysis of oils and fats with methanol, ethanol or propan-l-ol. With the growth in the hydrocarbon chain length of the alcohol, the lipophilicity increases so that the two-phase system does not form in the reaction with propan-l-ol, and glycerol does not separate. Therefore, the industrially important esters, such as propyl or butyl esters as well as esters of secondary alcohols, can be only prepared by direct esterification of fatty acids with the appropriate alcohol. Methyl and especially ethyl esters can also be obtained by enzyme-catalysed alcoholysis using non-specific lipases. 

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