摘要:

AbstractAnalysis of uptake‐lipophilicity profiles of carbonylcyanide R‐phenylhydrazones (RC6H4NHNC(CN)2) inParacoccus denitrificansand leukemic P‐388 cells showed that in early stages the drug distribution proceeds as simple diffusion in a multi‐phase system. After 10 min of partitioning only attainment of a lipophilic‐hydrophilic equilibrium was detected without observable chemical modification of the compounds. This fact allowed for straightforward formulation of two models for uncoupling of cellular oxidative phosphorylation, one based on protonophoric mechanism and the other involving covalent modification of energy transforming membrane proteins as the key step. Moreover, it enabled us to describe the dependence of uncoupling activity on lipophilicity using the uptake data and, thus, to reduce the number of adjustable parameters. The former (protonophoric) model exhibited a significantly better agreement with the experimental data in both b

ISSN:0931-8771    

DOI:10.1002/qsar.19880070402

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractPattern recognition techniques are applied to analyze the structure‐activity relationships (SAR) among α‐substituted‐β‐arylpropionic acid derivatives possessing hypolipidemic properties. The triglyceride lowering activity of 116 such compounds is investigated. Twelve structural descriptors are identified which can discriminate derivatives more active than clofibrate from those which have activity to or less than that of clofibrate with a success rate greater than 97%. Among the 12 descriptors selected out of a total of about 70, three are electronic and two are geometric. In addition, certain chemical substructures and their environments have been found to be important in determining the activ

ISSN:0931-8771    

DOI:10.1002/qsar.19880070403

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics and distribution of nine model acidic drugs (iodobenzoic, iodophenylacetic and iodohippuric acid derivatives) in rats were investigated following intravenous injection. The distribution volume of the central compartment increases linearly with increasing free drug fraction in plasma. Relatively weaker correlations were found between the distribution volume at steady‐state and lipophilicity or plasma protein binding. Even when a statistically relevant correlation between total plasma clearance and lipophilicity was found, this relation expresses rather the difference between individual acids. Comparing the individual position isomers, substitution of the aromatic ring with iodine in the para position leads to a strong decrease in the total plasma clearance value in contrast to a change in their lipophilicity. It shows that the total plasma clearance value is dependent not only on the lipophilicity, but on the geometry of drugs under study as wel

ISSN:0931-8771    

DOI:10.1002/qsar.19880070404

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe recently developed OASIS approachSee Refs. 1 to 4 for Parts I to IV of this series, as well as Refs. 6 and 7 for a detailed description of the approach.is applied to the modeling of substituted phenol toxicity. The best models derived show a certain contribution of the electronic factor in addition to the hydrophobicity factor; while the phenol geometric properties were found to be insignificant. The superdelocalizability indices characterizing the electron acceptor properties of the oxygen and its neighbouring carbon atom were found to be of importance along with the phenol acidity used in previous models and they can replace the latter in calculating substituted phenol toxicities. The complicated mechanism of the toxic agent‐receptor interaction is thus supposed to include some charge transfer from the biosubstrate to these two phenolic atoms with possible formation of a covalent or a hydrogen bond, although the charge‐controlled reactions seem to prev

ISSN:0931-8771    

DOI:10.1002/qsar.19880070405

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe intrinsic viscosities of solutions of a naphthalene derivative series i.e. quinoline, isoquinoline, 2‐methoxynaphthalene, 2‐naphthyl acetate, 1‐nitronaphthalene, 1‐naphthol and 2‐naphthol were determined in a series of aromatic solvents like benzene, toluene, anisole, pyridine, chlorobenzene and nitrobenzene. These magnitudes were correlated with various parameters which characterize solvents and solvent – solute interactions, the Lewis acidity and basicity, the Kirkwood function, the dipol moment, the molar polarizability, the function of polarizability as well as the Večeřa parameters. The polar solvation seems to be the predominating component of the solvent – solute effect in the case of quinoline, isoquinoline, 2‐methoxynaphthalene and 2‐naphthyl acetate whereas other factors become more important in case of the remaining compounds studied. The viscosimetric method appears to be suitable for the quantitative study of the solvent effect even if mainly Van der Waals forces are involved in the solvent – solute interactions and molecular weight of solute reaches h

ISSN:0931-8771    

DOI:10.1002/qsar.19880070406

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19880070407

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19880070408

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19880070409

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19880070401

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY