摘要:

AbstractNew successful applications of the Hansch‐type traditional QSAR to key steps in designing novel bioactive compounds are reviewed. Studies for a benzhydrylbenzylpiperazine antimigraine agent (lomerizine), azole‐type agricultural fungicides (metconazole and ipconazole), and a biphenylyloxobutanoic acid antiinflammatory agent (flobufen) were taken as the examples. Structural optimizations were nicely made by using the QSAR information sometimes along with findings obtained from 3D molecular modelling studies and/or hypotheses proposed for metabolic fates. The two azole fungicides were launched in 1994. The antimigraine and antiinflammatory agents are expected to be commercialized s

ISSN:0931-8771    

DOI:10.1002/qsar.19970160202

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractWHIM descriptors are 3‐dimensional molecular indices that represent different sources of chemical information. WHIM descriptors contain information about the whole 3D‐molecular structure in terms of size, shape, symmetry and atom distribution. These indices are calculated from (x, y, z)‐coordinates of a molecule within different weighting schemes in a straightforward manner and represent a very general approach to describe molecules in a unitary conceptual framework. A set of 40 simple heterogeneous compounds is used to show the main characteristics, some properties and the modelling power of WHIM descriptors by using simple scatter plots of the descriptors, Principal Component Analysis and predictions of simple physicochemical prope

ISSN:0931-8771    

DOI:10.1002/qsar.19970160203

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThree‐dimensional molecular indices (WHIM descriptors), proposed in Part 5 [1] are used to search for quantitative structure–activity relationships to investigate the physico‐chemical properties and biological activities of different classes of environmental important compounds.Chlorobenzenes are studied for their interesting physico‐chemical properties, e.g., melting and boiling points, solubility, lipophilicity (log Kow), bioconcentration factor (BCF), and for toxicity (Microtex test and algae). The antagonism of N,N‐dimethyl‐2‐halo‐phenethylamines to epinephrine and histamine is successfully modelled and compared with other models in the literature. Finally, good QSAR models are obtained for modelling the receptor binding affinities (RB) and inductions of aryl hydrocarbon hydroxylase (AHH) for some dioxin analogue compounds, polyhalogenated aryl derivatives.All the obtained models confirm the high modelling power of the W

ISSN:0931-8771    

DOI:10.1002/qsar.19970160204

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe applicability of multivariate statistical methods for the systematic analysis of results from the site‐directed experiments was tested. Dehalogenation data obtained with 15 single‐point mutants of haloalkane dehalogenase ofXanthobacter autotrophicusGJ10 has been related to various physico‐chemical properties of substituted amino acids. A two component model which explains 84% of activity data was derived. The most influential properties, required on position 172 in haloalkane dehalogenase were: aromaticity, main‐chain flexibility, refractivity and bulkiness, and were related mainly to the transition state/halide stabilization. The general usage of multivariate techniques for quantitative structure‐function relationships (QSFR) and protein engineering studies can be recommended. Score and loading plots from Principal Component Analysis (PCA) of physico‐chemical properties of amino acids can be used for planning and design of site‐directed mutagenesis experiments, while the models obtained from Projection to Latent Structures (PLS) can provide predictions on the effect of the mutations on protein functionality prior t

ISSN:0931-8771    

DOI:10.1002/qsar.19970160205

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe conformational analysis of two prolyl‐endopeptidase (PEP) inhibitors was performed. A molecular mechanics based random conformational search showed that 4‐phenyl‐butyryl‐prolyl‐pyrrolidine (1) is U‐shaped in most low‐energy conformations. The results were compared with semiempirical AM1 calculations. In contrast, the molecule octanoyl‐prolyl‐pyrrolidine (2) has a linear alkyl‐chain, although the U‐shaped conformations, required for the same mechanism of action, can be easily attained. The results of conformational analyses were compared with those of NMR measurements. The common pharmacophore for these and several other PEP i

ISSN:0931-8771    

DOI:10.1002/qsar.19970160206

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160208

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160209

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160201

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY