摘要:

AbstractA conformational analysis on calcium antagonists with diphenylalkylamine and diphenylbutylamine structure was performed based on force field calculations. Superposition of all energetically permitted conformations of all compounds under study led to the development of a common pharmacophore for both diphenylalkylamines (DPAAs) and diphenylbutylpiperidines (DPBPs). The pharmacophore consists of a – under physiological conditions protonated – nitrogen atom and three aromatic substructures. Conformational calculations on the verapamil derivative S( — )‐D595 and perhexiline showed that both substances possibly also interact with the DPAA/DPBP

ISSN:0931-8771    

DOI:10.1002/qsar.19890080402

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractAmphiphilic drugs of various structures are known to interact with phospholipids. Simple benzylamines have been used as probes to test the structural influence on the degree of interaction. This interaction has been quantified with various methods as for example NMR‐binding measurements, scanning calorimetry, inhibition of Ca++‐incorporation, negative inotropic effect and antimycobacterial activity.Multiregression and multivariate data analysis have been performed and the results are discus

ISSN:0931-8771    

DOI:10.1002/qsar.19890080403

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractThe partition coefficients for 123 furans, thiophenes, pyrroles and their benzofused derivatives are listed and the results discussed in terms of Δπ,i.e.the difference in π‐value from that expected for benzene. The smaller internal bond angle of 5‐membered rings leads to characteristically larger π‐values for some bulky groups, notably tertiary amide, since these can approach planarity more closely than in benzene. By contrast, lone pair repulsion lowers π for some 2‐substituted furans. Otherwise, π is very slight in furans and thiophenes, demonstrating the absence of appreciable electronic interactions. Because pyrroles and indoles are proton donors, they superficially show electronic effects similar to anilines. Closer analysis, based partly on the existence of anomalous negative Δπ values, demonstrates complications which the CLOGP algorithm does not consider. The rationale of electronic interaction and its effect on logPis discussed in terms of the need to consider (a) separate proton donor and acceptor terms, (b) rises as well as falls in lone pair electron density. It is pointed out,inter alia, that π‐donor ring hetero‐atoms are not proton acceptors, and that aromatic ring hetero‐atoms in general do not behave like ring substituents. While no attempt is made to construct an alternative algorithm, various suggestions are made concerning the lines along which C

ISSN:0931-8771    

DOI:10.1002/qsar.19890080404

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractAn integrated set of experimental methods is described which allows the determination of octanol/water partition coefficients for compounds of diverse structural type having log P values in the range – 1.3 to +4.6. This set has the advantage over a single technique of extending the scope and/or efficiency of log P measurement. A series of defined procedures for selecting the most appropriate method for a particular compound is described.The methods, which are all modifications of established techniques, are described in detail. The “Filter Chamber” technique is a quick and accurate method for log P measurement in the range ˜ −1.3 to +2.8. The “Spectrophotometric pH Profile” allows the “Filter Chamber” range to be extended to ˜ +4.6 by measurement of the extent of partitioning at pH values where the compound is partially ionised. The third technique, “Potentiometric Partition”, relies on potentiometric rather than spectrophotometric detection and hence has applications in determination of the log P of compounds with no chromophore. Each method is exemplified by measurements on simple organic molecules having known

ISSN:0931-8771    

DOI:10.1002/qsar.19890080405

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractStructure‐activity models are established using molecular connectivity indexes for the molar refraction of 115 alkylsilanes containing 10 monoalkyl‐, 14 dialkyl‐, 32 trialkyl‐and 59 tetraalkylsilanes. In the model based only on1χ, r = 0.997, s = 1.47, F = 20367. For the two indexes,1χ and2χv, r = 0.9987, s = 1.020 and for the three‐variable model based on0χv,1χ and2χv, r = 0.9994, s = 0.664. The quality of these models, based on the Kier‐Hall valence delta formalism, suggests the adequacy of that formalism in encoding the atomic characteristics of silicon in this data set. As a further test of the formalism, a mixed data set of 46 alkylsilanes, 46 alkanes and 41 chloroalkanes was investigated. For the same three indexes,0χv,1χ and2χv, r = 0.9996, s = 0.369. To reduce the intercorrelation between the two low order chi indexes, a linear transformation of these variables is introduced. The sum of a simple and valence index is used in place of the indexes themselves. The quality of the correlations is essentially the same using these sum variables. These results are compared to a proposed empirical modification of the valence de

ISSN:0931-8771    

DOI:10.1002/qsar.19890080406

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractTwo sets of the topological indices, i.e. molecular shape and molecular connectivity were calculated for a group of model hydrocarbons.Intercorrelation between these indices for five different sets of compounds was discussed.

ISSN:0931-8771    

DOI:10.1002/qsar.19890080407

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080409

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080410

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080401

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY