Moiety lipophilic

The partition coefficient P, defined as the equilibrium concentration of the compound in n-octanol divided by that in the aqueous phase, has been measured for pyrazole and indazole (B-79MI40416). It was found that log F = 0.13-0.26 for pyrazole and 1.82 for indazole, clearly showing the greater hydrophobicity (lipophilicity) of the indazole ring, due to the benzenoid moiety. 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

Molecules consisting of polar and apolar moieties behave as amphiphiles they are simultaneously hydro- and lipophilic or hydrophilic and hydrophobic. Due to this... 

Cholanic acid also possesses the ability of transporting cations across a lipophilic membrane but the selectivity is not observed because it contains no recognition sites for specific cations. In the basic region, monensin forms a lipophilic complex with Na+, which is the counter ion of the carboxylate, by taking a pseudo-cyclic structure based on the effective coordination of the polyether moiety. The lipophilic complex taken up in the liquid membrane is transferred to the active region by diffusion. In the acidic region, the sodium cation is released by the neutralization reaction. The cycle is completed by the reverse transport of the free carboxylic ionophore. 

By considering the stability constant and the lipophilicity of host molecules, Fyles et al. synthesized a series of carboxylic ionophores having a crown ether moiety and energetically developed the active transport of alkali metal cations 27-32). Ionophores 19-21 possess appropriate stability constants for K+ and show effective K+-selective transports (Fig. 5). Although all of the corresponding [15]crown-5 derivatives (22-24) selectively transport Na+, their transport rates are rather slow compared with... 

Lipophilic ligands, e.g. 45-49 having chiral L-2-pyrrolidine-methanol moieties, have been prepared and examined for their catalytic activities in reactions with optically active esters (50-52). 

As schematically shown in Fig. 1C, a carrier is an amphiphilic molecule capable of residing at the membrane aqueous interface with its lipophilic side interacting with the lipid of the membrane, with polar moieties directed outward into the aqueous phase, and with the polar moieties of a chemical nature to induce an ion into interaction. In the process of a carrier interacting and complexing with the ion, it... 

Local Anaesthetics. Figure 1 Common structure of local anaesthetics. A lipophilic moiety on the left, an aliphatic spacer containing an ester or amide bond in the middle and an amine group on the right are the typical structural elements for local anaesthetic drugs. 

In the first step bromocriptine 2 is isomerized to 2a, followed by an attack on proline ring in aminocyclol moiety of the molecule (formation of a new double bound on lO -ll, and bromination). This dibromo-compound 5 is brominated additionally on C-2 -propyl group. Tribromo-compound fi is very lipophilic and practically devoid of pharmacological activity. Hydroxy group and amide groups remain intact after all these reactions. 

Polymers conjugated with 1-adamantyl moieties as lipophilic pendent groups can be utilized to design nanoparticulate dmg delivery systems. Polymer (1) in Fig. 26, which is synthesized by homopolymerization of ethyladamantyl malolactonate, can be employed as highly hydrophobic blocks to construct... 

Neutral gangliolipids from Thermoplasma acidophilum were separated by PTLC, and their tentative structures were characterized by the combination of GC, H-NMR, and FAB-mass spectrometries [91]. The lipophilic portion of the neutral glycolipid was composed of caldarchaeol (dibiphytanyl-diglycerol tetraether), and the sugar moieties of the glycolipids were composed of glucose. 

Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic environment. It is commonly measured by its distribution behavior in a biphasic system, either liquid-liquid (e.g. partition coefficient in 1-octanol-water) or solid-liquid (retention on reversed-phase high-performance liquid chromatography or thin-layer chromatography system). 

Caron, G., Gaillard, P., Carrupt, P. A., Testa, B. Lipophilicity behavior of model and medicinal compounds containing a sulfide, sulfoxide, or sulfone moiety. 

The Jamieson paper reports the results of a number of studies, some successful, others not. Failures can be ascribed to the difficulties encountered in log P control. The first evident trouble concerns the choice of the lipophilicity descriptor many prefer log P, but this choice is questionable as has been outlined by Lombardo (see Chapter 16). Secondly, variations in lipophilicity profile influence not only hERG activity, but also target selectivity and also ADMET properties. Lipophilicity is a bulk property and its modification can involve different moieties of the molecules. Once the chemical modulation has been designed, but before moving to the bench, the research group should predict the consequences of this change on each step of the drug s action, but unfortunately this is not always done. 

QUESTION Substitution of lipophilic moieties on the phenyl ring of DOM makes the compounds more potent. Substitution of ionic-type moieties, like hydroxyl anions, makes them less potent. Is that a good generalization, that making the phenyl ring more lipophilic makes the compounds more potent in the DOM series ... 

Tarzia et al. [69, 70] have recently reported the FAAH inhibitory activity of a series of alkylcarbamic acid aryl esters. The starting point for their studies was the known serine hydrolase inhibitor carbamyl (51) that had no activity at FAAH. Replacement of the small methyl group of carbamyl (51) with more lipophilic groups and, in particular, bulky lipophilic groups resulted in increased affinity at FAAH (Table 6.6). Exploration of replacements of the naphthyl moiety revealed that replacement with a biphenyl group resulted in improved affinity and in particular, the 3-biphenylyl group proved effective... 

---