摘要:

AbstractPhorbol esters are polyfunctional agents which influence the carcinogenic process via a receptor mechanism. Two structural elements of phorbol esters seem to be responsible for tumor promoting activity. One element is formed of certain hydrophilic groups which are supposed to be responsible for the specific receptor binding. The other element consists of hydrophobic groups which should rather unspecifically be responsible for partition and transport between biological phases. In order to differentiate between these two structural elements, the numerical relativ tumor promoting activity of phorbol diesters (a new activity in QSAR) was calculated from rodent skin painting experiments and its dependence from hydrophobicity was modeled using the parabolic and the bilinear model. The results show that the tumor promoting activity of aliphatic phorbol 12,13‐diesters can adequately be described by hydrophobicity only. This indicates that the structural element aliphatic‐12,13‐diesters is rather unspecifically responsible for partition and transport between biological phases. A medium hydrophobicity caused by aliphatic ester chains in position 12 and 13 of phorbol is a sufficient condition for high promoting activity as long as the other hydrophilic groups are not removed, acylated or otherwise ch

ISSN:0931-8771    

DOI:10.1002/qsar.19900090102

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractUpper respiratory tract irritation of male Swiss OF1mice by airborne chemicals is well correlated by the following equations for the toxicity of nonreactive compounds,FRD′50is the concentration in mol 1−1of the airborne chemical required to elicit a 50% decrease in respiratory rate, and the explanatory variables are δ2a polarisability correction term, π 2*the solute dipolarity, α 2Hthe solute hydrogen‐bond acidity, Vxthe characteristic volume, and L16the gas/hexadecane partition coefficient. These equations considerably resemble corresponding equations for gas/liquid partition coefficients into organic bases such as tricresylphosphate, but do not resemble an equation for gas/water partition

ISSN:0931-8771    

DOI:10.1002/qsar.19900090103

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractRelationships between octanol/water partition coefficients (Kow) and parameters for molecular surface area or molecular volume are examined with new Kowdata determined by the slow‐stirring method. It is shown that Kowvalues of chlorobenzenes (PCBz's) and polychlorinated biphenyls (PCBs) can be described well using a single parameter regression equation. However, separate equations are established for the different groups of compounds. For 18 PCBs a very significant equation was obtained using data for the solvent accessible surface area (SASA) that was calculated according to a full quantum chemical geometry optimization of the chemicals. With a corrected shorthand method for the calculation of the total molecular surface area (TSA) or volume (TMV), also very significant relationships were obtained.An attempt was made to combine the Kowdata for both PCBz's and PCBs within one equation by adding the solvatochromic parameters. However, there remained differences between the experimental and calculated results for the chlorobenzenes and the PCBs.All linear correlations showed a deflection from the calculated values at high molecular areas or volumes which is probably caused by a solubilizing effect of the octanol present in the aqueous phase. Based on these observed deflections we estimate that the octanol/water partition coefficient (log Kow) will not exceed a value of

ISSN:0931-8771    

DOI:10.1002/qsar.19900090104

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractExperimental and calculated data of drug lipophilicity, i.e. octanol/water partition coefficients (log Pobs) and hydrophobic fragmental constants (Σf, C log P) have been compared for the following four groups of drugs: antiarrhythmics (AA), β‐blockers (BB), phenothiazines (PT) and benzamides (BA).Measured log P values indicate significantly varying lipophilicity ranges in the case of these four groups (AA>BB>BA>PT).Comparison of the two calculative approaches with observed log P values yields almost identical qualities. Strongest discrepancies between calculative and experimental data are discussed on the basis of putative experimental pitfalls or in relation to structurally derived miscalculati

ISSN:0931-8771    

DOI:10.1002/qsar.19900090105

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractThe quantitative structure‐activity relationship (QSAR) has been studied for the derivatives of 3‐aryl‐4,5,6,7‐tetrahydropyrazolo[4,3‐c]pyridine for their in vitro ability to displace [3H]prazosin. The physicochemical parameters, hydrophobic (π), and electronic (σ), and the structural parameter, van der Waals volume (Vw) are found to be significantly correlated with the displacement activity of thes

ISSN:0931-8771    

DOI:10.1002/qsar.19900090106

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractDifferent chromatographic data sets for hydrocarbons, alcohols, aldehydes, ketones, esters and barbiturates picked up from the literature were correlated with the kappa molecular shape indices. All correlations were statistically highly significant. Application of the kappa indices in such modelling is discussed.

ISSN:0931-8771    

DOI:10.1002/qsar.19900090107

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090108

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090109

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090110

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090101

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY