ISSN:0931-8771    

DOI:10.1002/qsar.19940130102

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the search for a better model of the rate limiting processes in peptide transport we studied the partitioning of solutes between heptane and ethylene glycol. Methods for determining the log partition coefficient (logPH/G) in this solvent system were developed and the reproducibility and ruggedness of such determinations were assessed. The partition coefficients in this system were found to correlate (r2= 0.86, n = 11) with the permeability coefficients for a group of model peptides. To understand the physical forces governing this partitioning process, the influence of four solvatochromic parameters: hydrogen bond donor strength (α) hydrogen bond acceptor strength (β), polarity (π*), and molecular volume (V1), was evaluated for a set of 20 benzene derivatives. Multiple regression analysis revealed that the solute hydrogen bonding parameters, especially α, were the most important determinants. Molecular volume of the solute was about half as influential compared with partitioning systems in which water is the polar phase. These results suggest that the requirement for hydrogen bond breaking is the principal deterrent to peptide transport and that log PH/Gis useful in predicting permea

ISSN:0931-8771    

DOI:10.1002/qsar.19940130103

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractA new approach to identifying descriptors associated with biological activity in ‘asymmetric’ data sets has been developed for high dimensional QSAR problems. As an example we have applied this approach to a problem first described by Selwood et al. [3]. Using Cluster Significance Analysis (CSA) in an explicit predetermined sequence of steps, we identified six likely determinants of antifilarial activity among antimycin analogs characterized by 53 descriptors. These determinants were ATCH5, ATCH2, VDWVOL, S8_1DX, ATCH4 and DIPV_X. Of them, only ATCH5, ATCH4 and DIPV_X were significant (R = 0.83) in a stepwise multiple regression analysis (MRA). These results are compared with those of the original workers and others who analyzed the data by different methods. By combining these descriptors with those identified by the other groups, we discovered a still better correlation. Jointly, ATCH5, ATCH4, DIPV_X, LOGP and MOFI_Y correlate highly with antifilarial potency (R = 0.91). The problem of discovering the ‘true’ determinants of biological activity in high dimensional asymmetric data sets is di

ISSN:0931-8771    

DOI:10.1002/qsar.19940130104

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThis report compares the results of QSAR analyses examining a series of bis(1‐aziridinyl)‐p‐benzoquinones using multiple linear regression (MLR), neural networks and a network hybrid technique known as a functional‐link net (FUNCLINK). The FUNCLINK approach generates an expanded list of new parameters and seemed to outperform MLR as well as providing an apparently superior predictive ability. One observation from this work showed that neural networks generated higher correlation coefficients than MLR. This phenomenon, however, may be due to the inability of neural networks to predict values beyond their operating range. On examination of the results it appears that there are two disadvantages to the FUNCLINK technique. Firstly, the natural ability of neural networks to develop non‐linear relationships is removed with FUNCLINK as these must be specified. Secondly, the large number of enhanced parameters produced by FUNCLINK must increase the possibility of chance effects. From the results presented here it would appear that FUN‐CLINK adds little to the field of QSAR da

ISSN:0931-8771    

DOI:10.1002/qsar.19940130105

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractA classification model based on 36 compounds inducing allergic contact dermatitis and 36 non‐allergens was developed by the discriminant technique of two‐value multiple regression analysis. One outlier was observed and several of the compounds fell in the indeterminate region between the classes. Based on variable results of clinical data (human and animal), some overlap in the model was considered more reasonable than perfect separation. The descriptors in this model clearly imply intercellular transport (LogP derived) and various forms of binding (London forces [MR] and hydrogen‐bonding [HBA, HBD]) as part of the allergic contact dermatitis (ACD) response mechanism. In addition, substructure descriptors related to the epidermal reactivity of the ACD inducers were statistically important. These include directly reactive functional groups from haptens and metabolizable precursor groups of prohaptens.The model was developed from carefully selected compounds of diverse structure, representing a broad range of hapten and prohapten substructures without undue molecular complexity. Validation of the model is in progress on a broad range of molecular structures far beyond those used in constru

ISSN:0931-8771    

DOI:10.1002/qsar.19940130106

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractWe present here a software that generates an extended connectivity matrix from the SMILES code of a molecule. This extended connectivity matrix allows the determination of the atomic code for an atomic fragment and then the attribution of its lipophilicity contribution fi. Then, log P can be easily computed by summing the fi values. This program which runs on IBM PC or compatible systems, can be used by chemists or pharmaco chemists interested in the fast evaluation of the lipophilicity of a series of molecules.

ISSN:0931-8771    

DOI:10.1002/qsar.19940130107

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThe lipophilicity (RM), specific hydrophobic surface area and the relative strength of interaction between trimethyl‐β‐cyclodextrin and 39 nonionic surfactants having different hydrophobic moieties has been determined by charge‐transfer thin‐layer chromatography using methanol as an organic modifier. RMvalues decreased linearly with increasing concentration of methanol. The significant correlation between the RMvalue extrapolated to water and the specific hydrophobic surface area indicates that these surfactants can be considered from the chromatographic point of view as a homologous series of solutes independently of their structural inhomogeneity. Stepwise regression analysis suggested that the length of alkyl chain in the hydrophobic moiety, the presence of sorbite and phenyl group in the surfactant molecule, and the number of ethyleneoxide groups per molecule have the highest impact on their hydrophobic parameters. The relative strength of surfactant‐cyclodextrin interaction significantly depended on the lipophilicity of the surfactants, and on the presence of phenyl group and ester bonds in the surfactan

ISSN:0931-8771    

DOI:10.1002/qsar.19940130108

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19940130109

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19940130111

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19940130112

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY