摘要:

AbstractThe pancreatic CCK antagonist activity of 73 benzodiazepines was studied by molecular modelling. Construction and optimisation by GenMol and MOPAC allowed us to obtain molecules of absolute minimum energy. Seven geometrical parameters and pharmacophores were selected for a processing by neuronal system. They allow a good prediction of activity of a compound belonging to this series: the correlation coefficients are 0.971 for the calculation and 0.952 for the prediction. A second database, limited to 23 compounds, constituted by a sample of the former one, allowed us, by selecting four parameters to obtain a satisfactory linear and not‐linear correlation for these compounds. The correlation coefficients obtained by neuronal system are 0.977 for the calculation and 0.967 for the predictio

ISSN:0931-8771    

DOI:10.1002/qsar.19970160602

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractInvestigations of the quantitative structure–activity relationships of a data set comprising 66 phenylalkanamines have been carried out using the CoMFA method. This yielded a cross‐validated correlation coefficient (q2value) of more than 0.8. The target parameter used was the hallucinogenic effect on humans, since this variable is of particular importance for research into addictive substances. It was possible to confirm the reliability of the CoMFA analysis by using a second, independent phenylalkanamine data set. It was found that models with good predictive properties are obtained if up to ten components are taken into account. In a further step it was possible to include hallucinogenic tryptamine derivatives in a common QSAR analysis with the phenylalkanamines and this in spite of their differing basic structures. The final model from that the CoMFA plots were extracted is based on 148 compounds and permits precise inferences to be made concerning the relationships between structural elements and hallucinogenic effe

ISSN:0931-8771    

DOI:10.1002/qsar.19970160603

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractMultiple linear regressions have been obtained for 49 psychotomimetic phenylalkylamines. The MTD method has been applied and the MTD parameter was used as steric descriptor. The energy of the lowest unoccupied molecular orbital and the net charges on the phenyl ring atoms (from AMI calculations) have been used as electronic descriptors and logPow, or average electrostatic field as lipophilicity descriptor. Hall and Kier electrotopological state indices were also tested. The descriptors have been scaled to unit and orthogonalized by Randic method. The predictability of the regressions obtained from MTD method have been checked by a method similar to cross‐validation from CoMFA method. MTD has been identified as the dominant descriptor by Randic orthogonalization. The best model has been obtained with MTD and electrotopological state indices, showing the importance of the steric and electronic properties for the interaction at the receptor site leve

ISSN:0931-8771    

DOI:10.1002/qsar.19970160604

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThis work will try to study an application example of quantum similarity measures, in order to determine quantitative relationships between the structure and biological activity for a family of steroids. The studied family is composed of 31 molecules, and the property analyzed is the affinity to the corticosteroid binding globulin receptor. Two methodologies have been chosen to perform QSAR on the mentioned steroid set. Both methodological frameworks are based on quantum similarity measures, the first one is based on the use of similarity indices as molecular descriptors and the second methodology uses quantum similarity topological indices for the same purpose. The use of molecular descriptors, obtained from quantum similarity topological indices constructs, constitutes a new technique developed recently in our laboratory to be used in QSAR in close relationship with the already explored field of quantum similarity measures. Results become comparable to other 3D‐QSAR technique

ISSN:0931-8771    

DOI:10.1002/qsar.19970160605

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractWe correlated skin absorption data, determinedin vivoin man under different experimental conditions for a set of 28 diverse chemical compounds, with experimental permeation constants (KpF) obtained for 8 compoundsin vitroon human skin, and with the calculated Kp (Kp QSAR) according to a modified Potts‐Guy algorithm.Fick's first law of diffusion was applied to calculatein vivopenetration constants Kpmax at the point of maximum flux Jmax.The occlusion variable shows a positive coefficient linking the degree of occlusion to larger logJmax permeation rates. The most significant correlation is seen for a sub‐set of 10 semi‐occluded applications of different compounds, with an r = 0.83 for logKpmax vs. logKpQSAR, and a somewhat lower value r = 0.79 for logKpmax vs. logKpF. We could thus demonstrate that a pseudo‐steady state presents a valid alternative to infinite‐dose dermal absorption conditions or predicted permeation values, even though Fick's postulated steady state is not achieved and the maximum flux value, Jmax, is use

ISSN:0931-8771    

DOI:10.1002/qsar.19970160606

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractPentamidine analogues bind to the minor groove by using thepharmacophoric conformationas being isohelical do DNA. A QSAR model has disclosed three physiochemical descriptors as being important for such compounds againstLeishmania mexicana amazonensis: Clog P, electrotopological index and Carbo similarity index. A comparison of the QSAR equation derived from multiple regression analysis, MRA, and the one from neural network analysis, NN, shows the latter to be of higher significance.

ISSN:0931-8771    

DOI:10.1002/qsar.19970160607

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160609

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160610

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160611

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160601

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY