摘要:

AbstractThe applicability of the comparative molecular field analysis (CoMFA) method to describe the electronic effects in 3D quantitative structure‐activity relationships (QSAR) has been investigated. Molecular fields calculated using an H+probe with the GRID force fields produced significant correlations with excellent cross‐validations. The CoMFA correlations were compared with the correlations of Hammett σ, σ+or σ–in the traditional biological QSAR. The results indicate that the CoMFA treatment of electronic effects using an H+probe as in this study are adequate for describing the corresponding effects in 3D QSAR

ISSN:0931-8771    

DOI:10.1002/qsar.19920110202

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractWe attempted to apply a new pattern recognition method called “functional‐link net” (Klassen and Pao, 1988) to QSAR. In contrast to the linear weighting produced by the generalized delta rule net often used in neural nets, the functional‐link net acts on a pattern element (a structural parameter in QSAR) or on the entire pattern itself to generate a set of nonlinear functions. In usual QSAR studies, linear forms of parameters are generally used. But, in many cases, parameters might contribute semilinearly to activity. Such a semilinear contribution of parameters can be examined by semilinearly transforming the parameters into a new parameter vector using a procedure with the architecture of the functional‐link net. The new method presented here was devised for analysis of QSAR from activity data given by a continuous variate. The application of this method to QSAR of several data sets of carboquon analogues with antileukemic activity gave better results than those given by multiple regression analysis of the same data sets. The comparison of the results with those given by the generalized delta rule net also showed that FUNCLINK was superior in the predictiv

ISSN:0931-8771    

DOI:10.1002/qsar.19920110203

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractFor studying the interaction of compounds with a receptor it is important to have a pharmacophoric model which describes the possible sites of interaction. The high flexibility of H2‐antagonists such as cimetidine, ranitidine and tiotidine hampered the definition of such a 3D interaction model for the H2‐receptor. However, for tiotidine a number of analogues are known which do not only have different substituents at various parts of the molecule, but which are rigid as well. This makes these compounds suitable for the purpose of defining a pharmacophoric model. Based upon a comparison of the various tiotidine analogues it was possible to determine four sites of interaction. Two receptor binding sites interact with the two NH2groups present in the 2‐guanidine group of tiotidine. The third site at the receptor interacts with the NH2group of the cyanoguanidine moiety which is connected to the ethylthiomethyl chain; this NH2group functions as a proton donor. The fourth binding site was found via a tiotidine analogue in which the flexible side chain had been replaced by a 4(5) imidazole group. One of the nitrogens of this imidazole ring functions as a proton donor. The orientation of this proton donor parallels the orientation of the proton donor function present in the cyanoguanidine group of tiotidine itself, leading to the suggestion that these two proton donor functions interact with the same receptor site. The results from these structural considerations, are summarized in a schematic model that can be used for subsequent studies on different groups of H2‐anta

ISSN:0931-8771    

DOI:10.1002/qsar.19920110204

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractSeveral sets of ligands acting as antagonists at muscarinic receptor sites are considered by means of QSAR approach. Although the confusing role of the collinearity among vectors associated with physicochemical parameters makes it sometimes difficult to evaluate the quality of structure‐activity correlations, the points discussed in the paper are to draw attention to the development of correlations between biological affinity constants and structural features of antagonists. The results obtained are compared to those relative to an analogous study on the agonists. It is shown that correlation equations are essential for deriving refined concepts on the topology of muscarinic receptor site

ISSN:0931-8771    

DOI:10.1002/qsar.19920110205

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractThe number of applications of computational techniques to medicinal chemistry is growing rapidly. Quantitative Structure‐Activity Relationships (QSAR) have been used very successfully to correlate structural features to biological activities. A type of QSAR, Linear Solvation Energy Relationships (LSER) has been used to correlate a large number and wide variety of biological properties. Famini and Wilson have developed a theoretical extension of the LSER, called the TLSER, that incorporates only computationally derived descriptors. We have applied the TLSER methodology to a series of fentanyl‐like compounds that exhibit activity at the opiate receptor. TLSER correlations of the entire data set, as well as specific subsets are conside

ISSN:0931-8771    

DOI:10.1002/qsar.19920110206

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractApparent ionization constants (pK aapp) of a series ofm‐andp‐substituted benzoic acids were measured by potentiometric titrations in an anionic micellar system (SDS, Sodium Dodecyl Sulphate). From these data, the binding constant K HABand the partition coefficient between micellar and aqueous pseudophases Pmic, were estimated for each derivative. Collander type regressions between log Pmicand log Poctare discussed. pK aappvalues correlate well with a linear combination of σ, πoctand MR molecular

ISSN:0931-8771    

DOI:10.1002/qsar.19920110207

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractA new algorithm is presented to analyze the structural features relevant to the biological activity of a set of molecules. The program called MULTICASE can, as its predecessor CASE (Computed Automated Structure Evaluator), automatically identify molecular sub‐structures that have a high probability of being relevant or responsible for the observed biological activity of a learning set comprised of a mix of active and inactive molecules of diverse composition. New, untested molecules can then be submitted to the program, and an expert prediction of the potential activity of the new molecule is obtained. MULTICASE differs from CASE in a great many ways, but the major algorithmic difference is the use of Hierarchy in the selection of descriptors, leading to the concept ofBiophoresandModulator

ISSN:0931-8771    

DOI:10.1002/qsar.19920110208

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19920110210

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19920110211

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19920110212

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY