摘要:

AbstractThe applicability of the comparative molecular field analysis (CoMFA) approach to describe the parabolic or bilinear dependence of biological activity on hydrophobicity in 3D quantitative structure‐activity relationships (QSAR) has been investigated. Molecular fields calculated with a H2O probe produced significant correlations with excellent cross‐validation. The results indicate that the CoMFA approach is an excellent methodology for describing nonlinear effects in 3D QSAR stud

ISSN:0931-8771    

DOI:10.1002/qsar.2660110302

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractWe devised a network with the “functional‐link net” architecture (Klassen and Pao, 1988) for QSAR for activity data given by ratings. Reference values used for training of the network were uniquely defined. In other neural networks such as the generalized delta rule net, reference values for activity ratings are usually defined by patterns using the combination of 1 and 0 so that more than one node is needed in the output layer.We, however, defined the reference by real values ranging from 0.0 to 1.0, thus, only one node sufficed in the output layer. Application of this network to QSAR of three data sets, 16 and 14 mitomycin derivatives with anticancer activity and 29 arylacryloylpiperazines with antihypertensive activity, gave good results. The comparison with other methods, such as ALS, FALS and the generalized delta rule net with back‐propagation of error, showed that our network is not only characterized by good recognition, but also by high prediction

ISSN:0931-8771    

DOI:10.1002/qsar.2660110303

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractFuzzy adaptive least squares (FALS91), a pattern recognition method for analyzing structure‐activity rating data to generate QSAR models, has been developed. A novel feature of FALS91 is that the degree to which each sample belongs to its activity class is given using a fuzzy membership function. This paper first describes the algorithm and calculation procedure of FALS91, and then shows its application to the correlation of structure with the activity rating of 31 calmodulin inhibitors and 29 α‐methylene‐γ‐butyrolactones with allergenic activity. Considerably high reliability was shown in both recognition and leave‐one‐out prediction of the FA

ISSN:0931-8771    

DOI:10.1002/qsar.2660110304

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractA simple computerized molecular structure scanning method was developed for generating a large, fixed number of calculated structural variables based on model structures derived from force‐field and quantum mechanics methods. These were reduced to one or a few parameters for QSAR studies by means of principal component analysis. When analyzed by principal component regression, the resulting descriptors summarize such gross features as electron distribution and substituent shape and volume very well. For two data sets (some substituted amphetamine hallucinogens and some dihydropyridine vasodilators), these calculated parameters were at least equivalent in their ability to model drug potency to those commonly used in QSA

ISSN:0931-8771    

DOI:10.1002/qsar.2660110305

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractAntifungal activities of a series of allylamines (Figure 1) were correlated with physicochemical parameters describing structural properties, such as lipophilicity, electronic distribution and steric requirements. A large number of physicochemical descriptors were calculated on the basis of a “possible” common conformation for all compounds studied. This conformation was deduced by crystallographic and theoretical studies. By an iteratively used, stepwise, multiple regression analysis (st‐MLR), the initial set of 27 descriptrs could be reduced to a number of 8–9 with only minimal loss of information content. Hence, three highly significant regression equations were established, indcating distinct requirements for the antimycotic activity against three different families o

ISSN:0931-8771    

DOI:10.1002/qsar.2660110306

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractIn this review article all relevant QSAR and molecular modelling studies that have been performed on both classical and non‐classical histamine H1‐antagonists are evaluated. Comparison of the results from these studies gives more insight into the physico‐chemical and conformational features that define receptor binding of H1‐antagonists. QSAR analyses indicate that at least seven classes of classical H1‐antagonists bind at the same receptor site. For these compounds a basic amino‐group, an aromatic ring (the so‐called “cis”‐ring) and a hydrophobic group (at the position of the so‐called “trans”‐ring) are essential for receptor binding. Similarities in the QSAR equations of diphenhydramines, mono‐phenyl analogues of diphenhydramines and benzimidazoles show that hydrophobic and steric factors are important for binding at the “trans”‐ring location. In literature it has been suggested that both aromatic rings of the non‐classical OPPI compounds can be superimposed in a folded conformation on the “cis”‐ and “trans”‐ring of the classical H1‐antagonist model. Although this idea remains interesting, QSAR data indicate that the proposed superimposition is probably not valid.Most molecular modelling studies performed on H1‐antagonists appear to have major draw‐backs: (1) e.g. only crystal structures were studied andor (2) antagonists were superimposed on the agonist histamine, whereas no experimental evidence is available that agonists and antagonists occupy similar receptor sites and/or (3) not all low energy conformations were considered. The most important conclusion that can be drawn from these modelling studies is that the optimal distance between the basic nitrogen atom and one of the aromatic rings is around 6 Å. Furthermore, two models of the H1‐antagonist binding site based on superimposition of antagonists on the classical semi‐rigid compound cyproheptadine are compared. It is concluded that cyproheptadine with the piperidylene ring in a boat conformatio

ISSN:0931-8771    

DOI:10.1002/qsar.2660110307

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractAn interactive receptor docking program has been implemented to facilitate computer modeling of the observed binding between N‐alkylbenzylamines and phospholipid vesicles.The computer modeling studies indicate that the aromatic portion of the benzylamines lies in close proximity to the phospholipid ester alkyl chains while the N‐alkyl groups may either project into the region occupied by the phospholipid head groups or fold back into the more hydrophobic environment. In this orientation, the interaction energies arising from a change in conformation with increasing N‐alkyl hydrophobicity correlate very well with experimental observations. This hypothesis was validated by NMR experiments in which two‐dimensional transferred nuclear Overhauser effects demonstrated that benzylamine N‐alkyl chains longer than five carbons bind in a folded con

ISSN:0931-8771    

DOI:10.1002/qsar.2660110308

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110309

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110310

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110301

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY