摘要:

AbstractA series of piperazine‐ and piperidine‐analogous propafenone derivatives was synthesized and tested for their ability to modulate PGP‐mediated multidrug resistance. A good correlation between lipophilicity and activity was obtained for a set of 13 compounds. Nevertheless, 4‐hydroxy‐4‐phenylpiperidines4a–dgenerally showed higher activity than predicted. A QSAR equation for the complete set of compounds was obtained when using both lipophilicity and an indicator variable for compounds4a–d(I=1; else I = 0) or H‐bond donor strength of the 4‐hydroxy group (rcv2= 0.90; n=17). Synthesis of aniline derivatives demonstrated that the propanolamine nitrogen interacts in protonated form. Studies on a series of diphenylalkylamines indicate, that steric factors also seem to play a role for the interaction of th

ISSN:0931-8771    

DOI:10.1002/qsar.19970160502

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractQuantitative structure–activity relationship (QSAR) studies are made on some nonbenzodiazepine ligands of benzodiazepine receptor (BZR), namely a series of 6‐arylpyrrolo[2,1‐d][1,5]benzo‐thiazepines, a series of pyrido[1,2‐a]benzimidazoles, and a series of some fused imidazopyridines. A Fujita‐Ban approach adopted for the first series led to the suggestion that the most advantageous substituents in the series were only 4‐Cl and 7‐OCON(CH3)2. All other substituents were found to have negative contributions to the binding of the compounds with the BZR. In the case of pyrido[1,2‐a]benzimidazoles, the 8‐CONHR group was found to play an important role in the binding. The activity was found to be significantly correlated with the hydrophobic property of the R moiety and the electron‐withdrawing ability of the ortho substituents in it. In the case of imidazopyridines, the Fujita‐Ban approach revealed only the negative effects of the substituents that really mattered. By Hansch analysis these negative effects were accounted f

ISSN:0931-8771    

DOI:10.1002/qsar.19970160503

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractQuantitative structure‐activity relationship (QSAR) studies, using the Comparative Molecular Field Analysis (CoMFA), on a series of 6,7‐diarylpteridine derivatives showing nematocide properties have been carried out. The CoMFA model generated in the study has been used to estimate the namatocide activity (MIC50) of seven 6,7‐diarylpteridines related to those previously studied. The model is highly predictive for all pteridine derivatives in the test set. Moreover, this model also predicts satisfactorily the nematocide activity of other [6] + [6]fused pyrazines (quinoxalines and pyridopyrazines) which were not represented in the training set. The analysis revealed the importance of steric factors (64.8%) and then the electrostatic ones (35.8%). Most pteridines under study were previously synthesized and tested as nematocide agents. Now, the synthesis and biological evaluation of 6,7‐di‐(2′‐thienyl)‐4(3H)‐thioxo‐pter

ISSN:0931-8771    

DOI:10.1002/qsar.19970160504

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe Hansch‐Fujita correlation analysis proved to be one of the major breakthroughs in the process of understanding relation between molecular properties and biological activity. In this approach the Hammett σ constants are used to characterize electronic effects of substituents. Experimentally determined σ constants have, despite their numerous very successful applications in QSAR studies, also some disadvantages, most notably availability only for limited set of substituents and not very good quality for uncommon functional groups. As an alternative the use of quantum chemical parameters is possible. In this article a methodology for theoretical estimation of Hammett σ constants is described, based on correlation with semiempirical atomic charges on the simple group attached to the substituent. The agreement with experiment for 63 most common organic substituents is good (r2= 0.89 for σmetaand 0.93 for σpararespectively, two‐parameters equation). As an example of possible application of this theory a World Wide Web‐based program for interactive calculation of electronic substituent constants is

ISSN:0931-8771    

DOI:10.1002/qsar.19970160505

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractIn QSAR analysis in environmental sciences adverse effects of chemicals released to the environment are modelled and predicted as a function of the chemical properties of the pollutants. Usually, the set of compounds under study contains several classes of substances, i.e., a more or less strongly clustered set. It is then needed to ensure that the selected training set comprises compounds representing all those chemical classes. Multivariate design in the principal properties of the compound classes is usually appropriate for selecting a meaningful training set. However, with clustered data, often seen in environmental chemistry and toxicology, a single multivariate design may be suboptimal. This because of the risk of ignoring small classes with few members and only selecting training set compounds from the largest classes. In this paper, a procedure for training set selection recognizing clustering is proposed. Here, when non‐selective biological or environmental responses are modelled, local multivariate designs are constructed within each cluster (class). The chosen compounds arising from the local designs are finally united in the overall training set, which thus will contain members from all clusters. Our illustration deals with a set of 66 compounds, categorized into five classes, for which the soil sorption coefficient is available. The training set selection is discussed, followed by multivariate QSAR modelling, model validation and interpretation, and predictions for the test se

ISSN:0931-8771    

DOI:10.1002/qsar.19970160506

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160507

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160508

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160501

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY