摘要:

AbstractThe applicability of the comparative molecular field analysis (CoMFA) method to describe the steric effects in 3D quantitative structure‐activity relationships (QSAR) has been investigated. Molecular fields calculated with a methyl probe produced significant correlations with excellent cross‐validation. These correlations are compared with the correlations of Es, STERIMOL parameter, and molecular volume (MV) in traditional QSAR. The results indicate that the CoMFA treatment of steric effects using a methyl probe is adequate for describing both the bulk and “steric” effects in 3D‐QSA

ISSN:0931-8771    

DOI:10.1002/qsar.2660110402

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractA quantitative structure‐activity relationship study on a set of anxiolytic benzodiazepines was carried out using the Hansch approach (QSAR) and the Comparative Molecular Field Analysis (CoMFA).The aim of the study was to investigate the nature of some of the main factors influencing the binding of the benzodiazepines to the CNS receptors. Since our preliminary QSAR results provided evidence of an involvement of a specific ligand‐receptor hydrophobic interaction, the methodological problem of how to properly include the scalar descriptor π in the development of the CoMFA model was extensively examined. The following explanatory variables were considered in the regression analyses: the HOMO and LUMO energies, the total dipole moment, the substituent constants π, ℐ, B1, B5, L, MR, the steric and the electrostatic CoMFA fields. The QSAR and the CoMFA were performed with Multilinear Regression Analysis and Partial Least Squares (PLS) Analysis, respectively. In each of the two methods the cross‐validation procedure was systematically applied to evaluate the significance of the correlation and to establish the most appropriate parametric dimensionality of the calibration models. A deeper insight into the meaning of the CoMFA electrostatic field as explanatory variable of the binding affinity was obtained by correlating the HOMO and LUMO energies with the electrostatic field itself. The results of this study suggest the existence of a specific interaction between the substituents which are in the “C7‐position”, formally corresponding to the 7‐chlorine atom in the structure of diazepam, and a receptor hydrophobic pocket. These substituents can additionally promote, through an electron‐withdrawing effect, a charge‐transfer interaction between the ligand and an electron

ISSN:0931-8771    

DOI:10.1002/qsar.2660110403

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractThe electrostatic properties of cimetidine and related histamine H2antagonists were studied by comparing their electrostatic potentials. The charge distribution of the cyanoguanidine moiety of cimetidine was calculated by various semi‐empirical molecular orbital methods, among which the electrostatic potential (ESP) derived charges in MNDO‐PM3 method were most significantly correlated withab initiocharges of 3‐21G basis set. Using the ESP charges, electrostatic similarities of each molecule compared with the most active compound were calculated according to the definition of Carbo and Hodgkin. The similarity indices obtained for the molecules superimposed by the least square fitting method were found to correlate with the H2antagonist activity, and the addition of logP term afforded more significant correlation, suggesting that the electrostatic similarity and lipophilicity of molecules are important for the activity. Furthermore, the superimposition of molecules to maximize the Carbo's similarity index was examined by SIMPLEX procedure. The result indicated that the superimposability both in steric and electrostatic properties is essential for the bioisosterism at the H2rec

ISSN:0931-8771    

DOI:10.1002/qsar.2660110404

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractOur model of the active site of the sweet taste receptor, defined by means of several rigid molds, such as saccharines and naphthimidazolesulfonic acids, already consistent with many classes of rigid and flexible sweeteners, is shown to be consistent also with the so‐called hypersweet molecules, notably guanidino‐acids and arylureido‐dipeptides, and with the crystal‐state structures of two conformationally restricted analogues of aspartame, alitame and [L‐(αMe)Phe]2aspartame, that have been recently

ISSN:0931-8771    

DOI:10.1002/qsar.2660110405

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractGeneralized Single Class Discrimination using Principal Component Analysis (GSCD‐PCA) is a novel method for the analysis of embedded biological activity. It is applicable to the analysis of a continuous activity measure and is suitable for multivariate data sets. It developed as a logical extension of Single Class Discrimination, which we recently described for the analysis of classified embedded biological activity. 4 different GSCD‐PCA algorithms are compared on artificial data sets containing parabolic and linear property‐activity relationships. 2 examples on structure‐activity data sets are given. The method performed well and produced stable, interpretable

ISSN:0931-8771    

DOI:10.1002/qsar.2660110406

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractA new method for estimating partition coefficients from data collected using the filter probe extractor (or similar equipment) is described.The method was developed to analyse the data from a two‐component mixture, which cannot be dealt with using the conventional form of data analysis. It is suggested that not only is this method suitable for mixtures but that it also offers advantages for pure compound

ISSN:0931-8771    

DOI:10.1002/qsar.2660110407

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

摘要:

AbstractNew potentiometrically‐based octanol‐water partition coefficient (log P) equations for di‐, tri‐ and tetraprotic weak acids are derived. These equations are valid when one or more species partition into the octanol phase as neutral or ion‐paired substances. Citric and phthalic acids were selected to demonstrate the log Pderivation procedure experimentally. Citric acid appears to participate in weak ion‐pair partitioning. Addition of tetra‐n‐butylammonium bromide to the solutions containing the weak acids, induces the hydrogen phthalate anion, the dihydrogen citrate anion and the hydrogen citrate dianinn to partition into octanol, presumably as ion‐pairs with the lipophilic cation. Extensive use is made of difference titration curves. The graphically derived models were refined by a general weighted nonlinear least

ISSN:0931-8771    

DOI:10.1002/qsar.2660110408

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110409

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110411

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.2660110412

出版商:WILEY‐VCH Verlag    

年代:1992

数据来源: WILEY