摘要:

AbstractIt is demonstrated that it is possible to obtain quantitative structure‐activity relationships from different molecular descriptors for the binding affinity of ten polycyclic aromatic hydrocarbons (PAH) for the rat liver 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) receptor, by the use of the partial least squares method. The variables used as descriptors range from theoretical and measured electronic properties to simple descriptors of the molecular geometry. A two component model, explaining 85% of the variance of the binding affinity of the ten PAH for the TCDD receptor is obtained when all descriptor variables are included in the analysis. When only molecular geometry descriptors are utilized in the modelling, a one component model explaining 75% of the variance is o

ISSN:0931-8771    

DOI:10.1002/qsar.19890080202

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractTo understand the role of the interaction between the positively charged quaternary nitrogen of the acetylcholine molecule and the anionic site of acetylcholinesterase, we measured the affinity of a number of aliphatic ammonium ions with bovine erythrocyte acetylcholinesterase in terms of the inhibition constant Kiand quantitatively analyzed the affinity index, log (1/Ki), with free‐energy‐related substituent and structural parameters and the multiple regression technique. Since the interaction of ammonium ions with the anionic site is regarded as being a type of ion‐pair formation in a hydrophobic milieu, we expected that the total steric effect of N‐substituents should be similar to that previously studied for the ion‐pair formation‐partition equilibrium of ammonium ions with picrate in the 1‐octanol/water system. By taking all of the steric effect terms in this ion‐pairing system as a single independent variable, the analysis was made to separate the specific hydrophobic effect of four N‐substituents on the affinity from their steric effect. The ammonium ions were suggested to interact with the anionic site so that the hydrophobic interaction of N‐substituents is dependent on their relative size while the total steric congestion is lowest. The hydrophobic nature of the enzymic milieu surrounding the anionic site was not uniform. The NH hydrogens in ions other than the quaternary were shown to lower the inhibitory activity nearly in proportion to their number. Being hydrated, the positively charged NH group could work to hold the ions in the bulk aqueous phase rather

ISSN:0931-8771    

DOI:10.1002/qsar.19890080203

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractExcellent structure‐molar refraction relationships of alkylphosphines, dialkyl sulfides, alkylthiols, alkylamines, dialkyl ethers, and aliphatic alcohols were obtained using the Randic molecular connectivity index. Excellent structure‐molar refraction relations were also obtained using two empirically‐modified connectivity indices which reflect either the difference in bond length between the heteroatom‐carbon bond and a carbon‐carbon bond or the difference in covalent radius between the heteroatom and a carbon atom. Use of the empirically‐modified indices improves the prediction of molar refraction for a mixed set of alkylphosphines, dialkyl sulfides, alkylthiols, alkylamines, dialkyl ethers, aliphatic alcohols, alkanes, alkylsilanes, alkylgermanes, and al

ISSN:0931-8771    

DOI:10.1002/qsar.19890080204

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractThe combination of the techniques of QSAR and Computer Chemistry (Quantum and Molecular Mechanics) has led to the generation of very large data sets, in terms of the number of parameters used to characterise the molecules of interest. Although there are techniques which may be used to analyse such data sets, it is recognised that there is considerable redundancy within these data. The computer routine CORCHOP was devised to aid the systematic reduction of such data sets to provide a parsimonius description whilst retaining their intrinsic information content. The use of this technique is illustrated by an example data set of antibacterial quinolones.

ISSN:0931-8771    

DOI:10.1002/qsar.19890080205

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractA quantum chemistry‐based strategy has been used for obtaining correlations between electronic parameters and the relative activity of some adenosine analogues that are substrates of adenosine deaminase. A semi‐empirical method (MOPAC program using AM1 hamiltonian) has been used for designing a molecule, alternative to adenosine, and less expensive from a computational point of view. It has been demonstrated that 9‐hydroxymethyl‐adenine effectively mimics adenosine behaviour in terms of electronic characteristics of purine ring. The parameters studied were net charge on N1 and C6, global (∑Q) charge over pyrimidine and purine rings and orbital frontier parameters over C6 and N1. For analogues of adenosine and formycin in which ribose were substituted by a hydroxymethyl group, correlations between these parameters and the log Vmof reaction (collected from experimental data) with adenosine deaminase have been studied. The results indicate that there is an increase in the maximum rate of deamination Vmwhen the negative net charge over the pyrimidine and purine rings also increases. In view of the results obtained with different forms (neutral, protonated at N1 and hydroxylated at C6) of adenosine and formycin analogues it is suggested that the protonation at N1 is the rate limiting step of the reaction catalyzed by adenosine

ISSN:0931-8771    

DOI:10.1002/qsar.19890080206

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractSeveral methods have been described in the literature for the calculation of weights which represent the contribution of fragments to the overall activity or inactivity of molecules which contain them. These weighting schemes are based on fragment occurrence data in training sets of molecules for which the activity is known. This paper reports a comparison of several such schemes (fourteen fragment weights in all), using small datasets for which structural and activity data are available. The comparison reveals that the most effective weight seems to be one derived from research into document retrieval systems (where indexing terms are used to discriminate between relevant and non‐relevant documents

ISSN:0931-8771    

DOI:10.1002/qsar.19890080207

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080208

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080209

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080201

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY