• Bulletin of the Korean Chemical Society
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• 제16권12호
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• pp.1189-1193
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• 1995

The comparative molecular field analysis (CoMFA) method has been employed to correlate the apparent lipophilicity (logkw) and global lipophilicity (logP) for orthopramide derivatives. This study demonstrated that CoMFA is an excellent method in predicting the complex properties of molecules such as apparent lipophilicity (logkw) or lipophilicity (logP). The better predictability of lipophilicity by introducing logkw as an independent descriptor suggests that the HPLC capacity factor measured in a buffer of pH 7.5 (logkw) can be effectively utilized in the prediction of global lipophilicity.

• Archives of Pharmacal Research
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• 제14권4호
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• pp.311-318
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• 1991

Corneal permeability of various n-alkyl p-hydroxybenzoates (parabens) was studied in vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S | $12{\phi}{\parallel}$) rensen's buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.

• Journal of Pharmaceutical Investigation
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• 제24권3호spc1호
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• pp.59-66
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• 1994

The objective of this study was to determine the influence of drug lipophilicity on the extent of ocular and systemic absorption following topical solution instillation in the pigmented rabbit. ${\beta}-Blockers$ of various lipophilicity were chosen as model drugs, $25\;{\mu}l$ of a 15 mM drug solution in isotonic pH 7.4 buffer was instilled, and ocular tissue and plasma drug concentrations were monitored. Ocular absorption was apparently increased in all eye tissues, but non-corneal absorption ratio was decreased by increasing of drug lipophilicity. Systemic bioavailability was ranged from 61% for atenolol to 100% for timolol, and at least 50% of the systemically absorbed drug reached the blood stream from the nasal mucosa. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol, but did not do so for atenolol and betaxolol. Taken together, the ocular absorption of topically applied ophthalmic drugs would be modest for lipophilic drugs. By contrast, the systemic bioavailability would be modest for drugs at the extremes of lipophilicity, and the nasal contribution to systemically absorbed drug diminished with increasing of drug lipophilicity.

• Bulletin of the Korean Chemical Society
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• 제21권10호
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• pp.951-952
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• 2000

Acylation of an intermediate tetrahydroxoplatinum(IV) complex, $[Pt(OH)_4(dach)]$ (dach = $trans-(\pm)-12-di-aminocyclohexane)$, with one or two kinds of carboxylic anhydrides in stepwise manner afforded various car-boxylatoplatinum(IV) complexes, $[Pt(O_2CR)\chi(OR’)4-\chi(dach)]$ (R = $(CH_2)_3CH_3$ or $C(CH_3)_3$, R’ = H or $OCCH_3$, and $\chi$ = 1-4) with a wide range of lipophilicity. The title complexes were subjected to bioassay using the murine leukemia L1210 cell line, and in particular, their in vivo oral antitumor activity was attempted to correlate with their lipophilicity and water solubility. The most orally active complex exhibited intermediate lipophilicity and water solubility, but it has been found that an exact relationship between the lipophilicity and oral anticancer activity could not be established, since the lipophilicity of the complexes is not the sole parameter to determine the oral activity. One of the important intermediate complexes partially substituted was subjected to X-ray anal-ysis for positit of the substituted group: $[Pt(OPiv)_3(OH)(dach)]$ crystallizes in the tetragonal sys-tem, space group $P42_1c$ with a = 21.161(3) $\AA$, b = 21.161(6) $\AA$, c = 12.816(3) $\AA$, $\alpha=\beta=$ r $=90^{\circ}$, V = 5739(2) $\AA^3$ and Z = 8.

• Environmental Analysis Health and Toxicology
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• 제14권3호
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• pp.103-111
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• 1999

To effectively predict the lipophilicity, the aryl hydrocarbon receptor (AhR) affinity, and TEF (Toxic equivalency factor) of dioxins by geometrical descriptors, the multiple linear regression methods with the forward selection and backward elimination were employed with statistical validity. The lipophilicity, the Ah receptor binding affinity, and the toxic equivalency factor of dioxins could be predicted using some geometrical descriptors.

• Archives of Pharmacal Research
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• 제17권3호
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• pp.182-189
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• 1994

The effect of lipophilicity on the mechanisms of drug absorption through biomembranes was investigated empolying HPLC system and the fluorescence technique. Human erythrocyte ghost membranes were used as a model biomembrane. A series of four parabens (methyl, ethyl, rpopyl, and butyl) and p-hydroxybenzoic acid were used as the model drugs for lipophilicities and their partition coefficients were measured in Sorensen's phosphate buffer solution (pH 5)/octanol system. Absorption amount of parabens through erythrocyte ghost membranes increased with an increase of lipophilicity resulted from the addition of methylene group to the n-alkyl chain of parabens. And the effect of parabens on the fluidity of ghost membrane also increased with an increase of their lipophilicities.

• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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• pp.43-51
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• 1995

The in vitro skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0,95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin, P-800) (40/60) lipophilic binary vehicle and an ethanol/water (60/40) hydrophilic binary vehicle with lauric acid, The skin permeability of the drugs was enhanced by the use of the ethanol/P-800 (40/60) binary vehicle or the ethanol/water (60/40) binary vehicle with lauric acid; permeation rate was increased and lag time' was decreased. The relationship between lipophilicity and skin permeation rate of the drugs showed parabolic shapes with their peaks at much greater hydrophilic range compared with other past references. In the in vivo skin absorption of theophylline using abdominal rat skin, the ethanol/P-800 (40/60)-7% (w/w) ethycellulose gel produced a good feature as a sustained-release preparation, and the ethanol/water (60/40)-3 % (w/w) HPMC gel with lauric acid showed the highest BA value. The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/P-800 (40/60) binary vehicle and ethanol/water (60/40) binary vehicle with lauric acid would be good candidates for clinical transdermal application of hydrophilic drugs.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.405-412
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• 2008

Six ester analogues of Ketorolac were synthesized as potential enhancer prodrugs for transdermal delivery. Solubility of these esters was determined in 10% propylene glycol (PG)/isotonic phosphate buffer (IPB) at room temperature while lipophilicity was obtained as partition coefficients (log P) and capacity factors (k') using HPLC. Stability of the prodrugs in skin extract and in plasma was investigated at $37^{\circ}C$. The lipophilicity of the potential prodrugs increased in proportion to their alkyl chain length. Good linear relationship between partition coefficients (log P) and capacity factors (log k') was observed ($R^2=0.9961$). All of the analogues were fairly stable but slowly degraded in IPB over a 12 hour period. However, their stability in skin extract and in plasma varied with most compounds gradually decomposing over a 12 hour period. Although unsaturation of the alkyl ester chain did not alter the over all lipophilicity of the compound, the half-life was significantly affected. In plasma, degradation of the esters was slower than in the skin extract, which is a desirable trait for enhancer-prodrugs. However, the overall hydrolysis in the skin extract needs to be facilitated for the development of an effective enhancer prodrug. The analogue with the shortest half life in the skin extract was the unsaturated C-12 analogue of 0.96 hr.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.158-161
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• 2003

Toxicity evaluations of 3-tert-butyl-, 2-isopropyl-, 3-isopropyl- and 4-propyl-phenol and their binary mixtures were performed with the Microtox$\^$(R) / assay and compared to invertebrates and fish. The single chemical, 4-isopropylphenol, exhibited the greatest relative toxicity to the Microtox organism (Vibrio fischeri). The relative electrophilicity (LUMO) of the phenols, in contrast to the lipophilicity (Log P), was strongly correlated with toxicity to V fischeri (r$^2$=0.96, p<0.01). In contrast, relative electrophilicity alone could not explain variances in toxicity of the phenols to Ceriodaphnia dubia. Results suggest that electrophilicity in conjunction with lipophilicity provide better correlation with toxicity to C. dubia and Pimephales promelas. Microtox results from the binary mixture toxicity tests of selected phenolics indicate a mechanism of interaction governed by suppression/antagonism.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2286-2300
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• 2011

We synthesized eight G8 molecular transporters (MTs) based on 4 different monosaccharide scaffolds, and studied their biological properties with a special focus on possible mitochondrial targeting and tissue selectivity. The mitochondrial affinity of these MTs was found to be clearly related to the scaffold stereochemistry and also tenuously with the lipophilicity. It may be suggested that in the practical delivery strategy of drugs for the brain and mitochondrial diseases the BBB permeability and mitochondrial affinity should be considered as key parameters, and that an enhanced mitochondrial affinity appears possible by further research on the structure-property relationship of guanidine-rich molecular transporters.