摘要:

AbstractA three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) was carried out on a set of 39 non‐congeneric muscarinic agonists using Comparative Molecular Field Analysis (CoMFA). The compounds were tested on the M3 receptor subtype. However, since most of these ligands are reported as unspecific muscarinic agents, the proposed pharmacophore model accounts for features common to all the receptor populations (M1, M2 and M3). In order to define an alignment rule for the superimposition of the ligands, a common pharmacophore frame was derived with a preliminary conformational search performed on four typical muscarinic agonists. Both the steric and the electrostatic fields were used in CoMFA as molecular descriptors and were found relevant with almost the same statistical weight. The CoMFA coefficient contour maps revealed consistency with our postulated mechanism of interaction.Several 3D‐QSARs were derived by means of the Partial Least Squares (PLS) method choosing the proper dimensionality with a cross‐validatio

ISSN:0931-8771    

DOI:10.1002/qsar.19910100402

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractGoodford's GRIN/GRID method is used for the prediction of protein antigenic determinants by calculation of the interaction energy between proteins and water. The comparison of the regions of high interaction energy for the proteins lysozyme, myohemerythrin and tobacco mosaic virus protein with experimentally determined contact surfaces in antigen‐antibody complexes and epitopes obtained by cross‐reactivity measurements shows remarkable agreement. Accessible surface regions of considerable attraction for polar probes seem to be of special importance for antigen‐antibody recogn

ISSN:0931-8771    

DOI:10.1002/qsar.19910100403

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractFour related QSAR models of teratogenesis in experimental animals have been developed: one each for heteroaromatic, carboaromatic, alicyclic and acyclic compounds. The numbers of compounds in these models range from 40 (for the alicyclic model) to 144 (for the carboaromatic model). As determined by cross‐validation using the leave‐one‐out, or jackknife, technique, the accuracy of the models in discriminating between teratogens and non‐teratogens ranges from 92.4% to 96%.A single overall assessment of experimental teratogenesis was chosen as the biological endpoint; taking into account such factors as dosage, maternal toxicity, and affected organ systems remain to be subjects of further

ISSN:0931-8771    

DOI:10.1002/qsar.19910100404

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractA chemometric approach based on multivariate calibration and design in latent variables permits one to rationalize the antibacterial activity of quinolones against gram negative bacteria, ranking the relative importance of individual structural features, and suggesting a new active structure.

ISSN:0931-8771    

DOI:10.1002/qsar.19910100405

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractA variety of techniques and methodologies are currently being used in quantitative structure‐activity relationships (QSAR). A major difficulty with past relationships has been the use of a parameter sets which cannot be applied uniformly to a wide range of properties and data sets. The development of the Linear Solvation Energy Relationship by Kamlet and Taft, and our development of the Theoretical Linear Solvation Energy Relationship (TLSER) have attempted to overcome this principal difficulty by employing a standard parameter set for every correlation. Another methodology that has also proven successful in this regard is the use of topological indices to correlate a variety of properties. This paper compares the TLSER with one such index, the molecular transform. In addition, we show the high correlative capability of the TLSER methodology with the minimum blocking concentration for a set of 36 local anesthetic

ISSN:0931-8771    

DOI:10.1002/qsar.19910100406

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractThe computer package EDISFAR is described. The programs can manage physico‐chemical information from a database (MONOBASE) of the fragment parameters classically used in drug design, providing assistance in the use of the techniques related with the Hansch‐Fujita analysis. The user can make design of exploring series of bioactive compounds, using a great variety of techniques, and once a QSAR model has been obtained, can calculate optimum derivatives using the parameters of the MONOBASE. The program has been designed emphasizing its flexibility, accessibility by the practical chemist, and compatibility with other statistics programs or comput

ISSN:0931-8771    

DOI:10.1002/qsar.19910100407

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

摘要:

AbstractSingle Class Discrimination using Principal Component Analysis (SCD‐PCA) has been developed to discriminate an embedded data class. The embedded class is defined as the active class and the diffuse class, or classes as the inactives. Two basic methods are described. Both involve an initial column centring and scaling of the data to the actives space. Method I then directly obtains the directions of maximum variance in the inactives by PCA, while method II attempts to maximize the ratio of inactives to actives variance using PCA. The methods offer good potential to reveal a tightly bedded active class near the origin with the inactives dispersed. Techniques to portray the discrimination power and significance of the PCs are discussed. SCD‐PCA has been applied to artificial data sets exhibiting a variety of distributional characteristics and to two QSAR data sets. The method performed predictably on the artificial data. Good, low dimensional PC models were obtained for the QSAR data sets which were stable when cross‐vali

ISSN:0931-8771    

DOI:10.1002/qsar.19910100408

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19910100409

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19910100410

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19910100411

出版商:WILEY‐VCH Verlag    

年代:1991

数据来源: WILEY