Highly lipophilic

Drugs. Ttifluoromethyl-based pharmaceuticals had been limited to phenothiatine tranquilizers and benzothiadiazine 1,1-dioxide diuretics (qv). However, new dmgs have been developed (Table 11). One of the key properties of the CF group is its high lipophilicity it increases the Hpid solubiUty of the pharmaceutical and thus accelerates absorption and transport within the host organism. 

Mode of Action. DDT and its analogues specifically affect the peripheral sense organs of insects and produce violent trains of afferent impulses that result in hyperactivity, convulsions, and paralysis. Death results from metaboHc exhaustion and the production of an endogenous neurotoxin. The very high lipophilic nature of these compounds faciUtates absorption through the insect cuticle and penetration to the nerve tissue. The specific site of action is thought to be the sodium channels of the axon, through inhibition of Ca " ATPase. 

Polyethers are usually found in both the filtrate and the mycelial fraction, but in high yielding fermentations they are mosdy in the mycelium because of their low water-solubiUty (162). The high lipophilicity of both the free acid and the salt forms of the polyether antibiotics lends these compounds to efficient organic solvent extraction and chromatography (qv) on adsorbents such as siUca gel and alumina. Many of the production procedures utilize the separation of the mycelium followed by extraction using solvents such as methanol or acetone. A number of the polyethers can be readily crystallized, either as the free acid or as the sodium or potassium salt, after only minimal purification. 

Itraconazole. Itraconazole (18) is a highly lipophilic compound with a triazole stmcture. Compared to ketoconazole, itraconazole has a broader spectmm (including yispergillus spp.) (29,30) and an in vitro activity that is 10 times higher than ketoconazole for most species. 

Stability. Avermectins are highly lipophilic substances and dissolve in most organic solvents such as chloroform, methylene chloride, acetone, alcohols, toluene, cyclohexane, dimethylformamide, dimethyl sulfoxide, and tetrahydrofiiran. Thek solubiUty in water is correspondingly low, only 0.006-0.009 ppm (= mg/L). 

In this work, the results of study of zinc thiocyanate complexes anion-exchange extraction by non-symmetric QASes in toluene ai e discussed. The non-symmetric QASes have the common formula [(C,3H g03)N(CH3) (C,H Q3 J-X-, where C,3H3 03 - highly lipophilic substituent, (2, 3, 4-tn. s-dodecyloxy)benzyl. It was found that exchange... 

M 644.9, m 156-158". Purified by chromatography on a Kieselgel column and eluted with CH2Cl2-EtOAc (5 1), and recryst from EtOH-Me2CO as colourless crystals. It is an electrically neutral ionophore with high selectivity for Ba " ions and with high lipophilicity. [Chem Ber 118 1071 1985.]... 

This highly lipophilic group is cleaved with isoamyl nitrite in Pyr/AcOH. The use of a lipophilic 5 -phosphate protective group aids in reverse-phase HPLC purification of oligonucleotides. 

This highly lipophilic tetracycline is the first "one-a-day" tetracycline (when used to treat mild infections). 

The passage of a small and/or highly lipophilic molecule through the membrane phospholipid bilayer according to the gradient of its concentrations across the plasma membrane. It is slower than facilitated diffusion, which, however, also follows the gradient of solute concentrations across the membrane. 

Excretory processes for xenobiotics are best understood for mammals, with far less work having been done on birds, reptiles, and amphibians. Highly lipophilic compounds show little tendency to be excreted unchanged. In the absence of effective metabolism, they tend to have very long biological half-lives in depot fat. Thus, half-lives of about 1 year have been reported for p,p -DDE in birds, whereas higher... 

Heroin (diacetylmorphine) a highly lipophilic drug but has very weak or no affinity for opiate receptors. It penetrates the brain rapidly whereupon it is metabolised to morphine which then binds to the mu receptor. 

As mentioned in last year s Report, aromatic phosphoramidates have been used to protect 5 -phosphoryl groups in the stepwise synthesis of oligodeoxyribonucleotides. The appropriate monomer units are coupled with DCC and the phosphoramidate protecting group is removed when required with isoamyl nitrite. A rapid and general preparative method for oligonucleotides has been developed based on phosphoramidates of the highly lipophilic 4-aminophenyltriphenylmethane (25). Purification of... 

Borel, R, Factors affecting intestinal absorption of highly lipophilic food microconstituents (fat-soluble vitamins, carotenoids and phytosterols), Clin. Chem. Lab. Med., 41, 979, 2003. 

Cannabinoids are highly lipophilic compounds making bioavailabihty very dependent on the formulation and the mode of administration. Cannabinoid occurrence in the plant is predominantly in the form of the carboxyhc acids, which are pharmacologically totally different and rather unstable, decarboxy-lating over time to their active neutral form. The carboxyhc acids, although not active at the CB receptor, nevertheless add to the overall effect as they possess antibiotic and anti-inflammatory effects. 

Highly lipophilic benzoxazoles with potential antibacterial activity, 36... 

Vinsova, J., Highly lipophilic benzoxazoles with potential antibacterial activity presented at 8th International Electronic Conference on Synthetic Organic Chemistry ECSOC-8. November 1-30, 2004. 

Steroids have long been used in the treatment of neurological injury. These highly lipophilic compounds have a high aflSnity for membrane bilayers. This property is key to their role in inhibition of lipid peroxidation. 

If the photoequilibrium concentrations of the cis and trans isomers of the photoswitchable ionophore in the membrane bulk and their complexation stability constants for primary cations are known, the photoinduced change in the concentration of the complex cation in the membrane bulk can be estimated. If the same amount of change is assumed to occur for the concentration of the complex cation at the very surface of the membrane, the photoinduced change in the phase boundary potential may be correlated quantitatively to the amount of the primary cation permeated to or released from the membrane side of the interface under otherwise identical conditions. In such a manner, this type of photoswitchable ionophore may serve as a molecular probe to quantitatively correlate between the photoinduced changes in the phase boundary potential and the number of the primary cations permselectively extracted into the membrane side of the interface. Highly lipophilic derivatives of azobis(benzo-15-crown-5), 1 and 2, as well as reference compound 3 were used for this purpose (see Fig. 9 for the structures) [43]. Compared to azobenzene-modified crown ethers reported earlier [39 2], more distinct structural difference between the cis... 

Such a parabolic relation has the following incidence on drug delivery a molecule with a low partition coefficient will partition slowly from water into a lipid membrane. If the receptor is within or beyond that membrane, such a molecule will have a low probability of reaching it in the time interval under study. Conversely, molecules which are highly lipophilic will readily partition into the first of a series of lipid membranes, but will be held there and thus slowed down in their random walk to their site of action. Hence, optimal transport conditions are clearly achieved by drugs of intermediate partition coefficient, with no transfer step being too low. 

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