摘要:

AbstractThe log P value of 53 N‐acetyl‐di‐ and tripeptide amides composed of amino acids having unionizable side chains was measured in a 1‐octanol/pH 7.0 aqueous buffer system. The factors governing the variations in the log P value among these protected peptides were quantitatively analyzed to formulate a correlation equation with free‐energy‐related physicochemical and substructural parameters. The log P value was governed by the sum of the hydrophobicity of side chains and the backbone as well as by the steric effects of side chain substituents on the relative solvation of the backbone CONH groups. The log P value was found to decrease by 0.6 log unit for the peptide bond, other factors being equal. For amino acids with polar side chains, the log P value was also affected by the “polar proximity factor” and/or intramolecular hydrogen bond formation in a way similar to that of zwitterionized peptides repo

ISSN:0931-8771    

DOI:10.1002/qsar.19900090302

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractThe conformational features of ten known amnesia reversal compounds were analyzed by the molecular mechanics calculations with the aim of identifying a common spatial disposition of the polar functional groups present in all the molecules (a N‐C=O amidic group and a X‐C=O group, with X = O, N). Principal component analysis (PCA) led to the identification of three interatomic distances able to provide all the information necessary to describe the relative spatial disposition of the two functional groups. Cluster analysis was then performed to group the minimum energy conformations according to the values of those distances. Clusters were analyzed to single out those containing conformations of the maximum number of active compounds. This procedure permitted the finding of several acceptable pharmacophore models. The influence on results by the dissociated/undissociated forms of carboxylic compounds presented in the data set is also discussed. Two potent prolyl endopeptidase (PEP) inhibitors showing strong anti‐amnesic effect were also included in the study. The results suggest that the common biological activity between these classes of compounds could be interpreted on the basis of the common spatial disposition of the investigated functional g

ISSN:0931-8771    

DOI:10.1002/qsar.19900090303

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractReceptor site binding is shown to be localized in selected atoms or substructures with relatively minor contributions from the remaining molecular framework.Related compounds can be overlayed to form a lowest common structure or hyper‐molecule that defines every possible binding site for the series. Any attempt to analyze binding data on an atom‐by‐atom basis would clearly fail if all or most of the positions were involved in the energetics. In most data sets, analysis becomes feasible when most of the variance depends on a minority of the total occupied positions. This appears to be the case in most of the sets analyzed to date, providing us with a unique opportunity. By using atomic descriptors to model lipophilicity, London forces, steric repulsion and charge interactions, the binding site can be mapped by regression analysis. Each important site of interaction and the nature of the binding force can be clearly identified. This procedure provides a statistical method based on measured data that fully complements the visual fitting of modeled drugs into defined receptor sites by computer graphics. It has enormous potential for analysis of drug, agrochemical and toxicological binding data where crystallized enzymes and fully defined sites are unknown and may long remain so.The method is illustrated by examples drawn from acetylcholinesterase receptor site bi

ISSN:0931-8771    

DOI:10.1002/qsar.19900090304

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractA substructural analysis of antineoplastic compounds is provided with respect to twoin vivotumor models: lymphoid leukemia L1210 (L1210) and Lewis lung carcinoma (LL). The activity data are expressed by 4 levels of activity against L1210 and LL. The structures of the compounds are described by means of structural features derived from a structure‐activity relationship (SAR) oriented language for two‐dimensional chemical structure representation. A statistical‐heuristic technique is applied to obtain, for each structural feature, a weight for each activity level. On the basis of the weights, the contributions of the structural features to the probabilities of activity against L1210 and LL models are estimated. The features contributing to the relevant probabilities to the greatest extent are located and analyzed from a biochemical point of view. The results obtained show the suitability of the features for compounds' activity recognition and identification of substructures significant for the investigated activ

ISSN:0931-8771    

DOI:10.1002/qsar.19900090305

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractIn cultured chick embryo hepatocytes, induction of cytochrome P450 by nine 5,5‐substituted barbiturates was analyzed for a quantitative structure‐activity relationship. The data led to the following equation: Log 1/C = 1.02 (±0.16) log P + 2.75 (±0.28), r = 0.984where C is the concentration that caused a 50% increase in cytochrome P450, P is the partition coefficient between octanol and water, and r is the correlation coefficient. The results suggest that the potency of the barbiturates was directly related to their hydrophob

ISSN:0931-8771    

DOI:10.1002/qsar.19900090306

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

摘要:

AbstractThe Wiener index W was defined originally for saturated hydrocarbons. In this work the definition of W was extended for unsaturated hydrocarbons: W = Ws+ Wd+ Wt+ Wa, where s, d, t, and a refer to the contributions of single, double, triple and aromatic bonds, respectively. Good correlation (r = 0.95) could be demonstrated between the logarithms of n‐octanol‐water partition coefficients of the molecules and the components Ws, Wd, Wtand

ISSN:0931-8771    

DOI:10.1002/qsar.19900090307

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090308

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090309

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19900090301

出版商:WILEY‐VCH Verlag    

年代:1990

数据来源: WILEY