ISSN:0931-8771    

DOI:10.1002/qsar.19880070302

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe Free Wilson model is a simple and efficient method for the quantitative description of structure activity relationships. It is the only numerical method which directly relates structural features with biological properties, in contrast to Hansch analysis, where physicochemical properties are correlated with biological activity values. Nevertheless both approaches are closely interrelated, not only from a theoretical point of view, but also in their practical applicability. In many cases both models can be combined to a mixed approach which includes Free Wilson type parameters to describe the activity contributions of certain structural modifications and physicochemical parameters to describe the effect of some other substituents on the biological activity. Many successful applications, especially from the work of Hansch and his group on the structure activity relationships of enzyme inhibitors, demonstrate that this combined model is the most powerful tool of classical QSAR.

ISSN:0931-8771    

DOI:10.1002/qsar.19880070303

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractPartition coefficient (P) is a widely‐measured property, yet there is considerable variation among published log P values. This paper examines the factors that can affect the measurement of partition coefficient, and makes recommendations as to good practice. Accuracy of partition coefficient determination can be affected by temperature, lack of mutual phase saturation, pH, buffer type and concentration, phase miscibility, solute concentration, solute and solvent purity, solute stability, phase volume ratio, solute adsorption and failure to reach equilibrium conditions. It is recommended that partitioning be carried out at constant temperature using either a stirred flask technique or the filter prob

ISSN:0931-8771    

DOI:10.1002/qsar.19880070304

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

Abstract48 amino acids (20 coded and 28 non‐coded) were multivariately characterized by seven thin layer chromatography variables and two theoretical variables (molecular weight and side chain van der Waals volume). Principal components analysis (PCA) of the original 48 × 9 data matrix, resulted in two significant principal components which together described 88% of the variance in the data. The relationship between these principal components and the earlier estimated z‐scales for coded amino acids was investigated. In addition, it was found that the principal components had a predictive capacity similar to the z‐scales, when compared in a peptide QSAR of a series of bradykinin potentiating pentapeptides modified with only coded amino acids. Thus it is shown that TLC is a rapid technique suitable for the parametrization of amino

ISSN:0931-8771    

DOI:10.1002/qsar.19880070305

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe relationship between chemical structure of a solute and the logarithm of its partition coefficient (log P) between the aqueous and a nonpolar phase is poorly understood. We have recently shown that the variation in log P data for 50 low molecular‐weight organic solutes in 6 aqueous‐non‐polar solvents is a function of two structural features. The main feature accounts for ≈︁60% of the variation in the log P data, and is uniformly weighted in all 6 nonpolar solvent systems. This suggests that it is related to the aqueous solution properties of the solute. The first feature is termed the isotropic surface area, or the surface area associated with the nonpolar portion of the solute when the solute is considered to be a hydrated complex. The hydrated solute complex is termed a supermolecule with waters of hydration occupying hydrogen bonding sites on the functional groups of the solute. Empirical rules for formation of the super molecule are discussed.In this report the analysis is extended to log P data for 72 solutes in the 6 nonpolar solvent systems. The results of the analysis are essentially unchanged for this more extended data set and the second factor is tentatively identified. The second structural feature accounted for ≈︁35% of the variation in the log P data was not equally weighted in all solvents and is difficult to interpret

ISSN:0931-8771    

DOI:10.1002/qsar.19880070306

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractA Free‐Wilson analysis of 95 digitalis‐like steroids inhibiting the Na/K‐ATPase is presented. The chosen parent structure – 5β,14β‐androstane‐3β,14‐diol – was varied at 12 individual substitution sites. The high significance of the multiple regression of the data obtained with the great majority of the derivatives tested revealed the general applicability of the additivity model, allowing the prediction of the potency of hypothetical compounds from the derived 57de novosubstituent constants. Derivatives carrying voluminous substituents at C3 or C17, in which the cis/trans/cis‐junction of the steroid rings were altered, disclosed incompatibil

ISSN:0931-8771    

DOI:10.1002/qsar.19880070307

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractThe toxic effects of ecotoxicologically relevant chemicals (phenols, anilines, aliphatic hydrocarbons) have been determined using several in vitro testing procedures which are assumed to represent relevant biological systems. These test systems selected within a collaborative study supply information about toxic effects on different levels of interference with ecosystems. Other selection criteria were reliability of the procedures, exact quantification of the observed effects, and low cost. Subsequently the toxicity data obtained in the different biological systems for more than 50 phenol‐, aniline derivatives and hydrocarbons were used to derive quantitative structure‐toxicity relationships. The regression equations obtained were compared. For all biosystems under study a dependence of toxic potency on the lipophilic properties of the compounds was found. With the same data set principal component analysis has been performed and the results give evidence that the ranking of toxicants is similar in the different testing systems used.These results are further supported by the analysis of literature data from test systems of various complex

ISSN:0931-8771    

DOI:10.1002/qsar.19880070308

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractBased on force field methods, quantum chemical calculations and using molecular graphics a hypothetical receptor model for calcium antagonists and agonists from the 1,4‐dihydropyridine (DHP) series has been developed. In a previous study it could be shown, that calcium channel activating DHP's reduced the molecular electrostatic receptor potential, while this is increased by calcium channel blocking DHP's. These effects offer a possible explanation for the opposite behaviour of chiral dihydropyridines. In continuation of this work a quantitative structure‐activity study with a group of calcium channel blockers provided a three binding site model for the drug receptor interaction. Calculated interaction energies correlate well with biological potencies (r = 0.94, s = 0.28). The postulated receptor model shows structural similarities to segments of the very recently published amino acid sequence of the receptor for 1,4‐dihydropyridine calcium channel blo

ISSN:0931-8771    

DOI:10.1002/qsar.19880070309

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

摘要:

AbstractFollowing preliminary observations on auxin‐like activity of several 1‐ and 2‐substituted benzotriazole isomers, a few new derivatives have been synthesized and tested. In attempting to quantify by QSAR the structural properties of a large set of compounds and with the aim to rationalize the structure‐activity relationships taken into account in a previous study by a set of indicator variables, attention was turned to the analysis of13C‐NMR and1H‐NMR chemical shifts relative to the substituent carbon atom attached on the nitrogen of the benzotriazole ring. The13C‐NMR chemical shift can be useful as an independent parameter in QSAR. Considerations of the general applicability of sigma inductive constants for predicting physicochemical properties of complex heteroaromatic systems such as those under study are discussed. Finally it is shown that there are important electronic and steric components which play a major role in promoting the auxin‐like activity of compounds un

ISSN:0931-8771    

DOI:10.1002/qsar.19880070310

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19880070311

出版商:WILEY‐VCH Verlag    

年代:1988

数据来源: WILEY