bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplified C‐13 NMR Parameters Related to the Carcinogenic Potency of Polycyclic Aromatic Hydrocarbons
Authors: Nordén Bo , Edlund Ulf , Johnels Dan , Wold Svante 
Published: October 2006

AbstractEleven polycyclic aromatic hydrocarbons (PAH) with known carcinogenic activity have been analyzed using a partial least squares (PLS) method. The analysis result using reduced C‐13 NMR parameters of protonbearing and non‐protonbearing carbons (chemical shift mean, variance, skewness and kurtosis) against the carcinogenic activity is compared with a similar analysis using 23 theoretical and measured variables. Similar structure‐activity trends were indicated in the two analyses, showing that C‐13 NMR parameters contain useful information.
Prediction of New Leads from a Distance Geometry Binding Site Model
Authors: Crippen Gordon M. 
Published: October 2006

AbstractIn a previous study, we derived a 9 point model of the binding site of S. faecium dihydrofolate reductase, given only the binding data for a set of 68 quinazoline inhibitors. We have now used this model to search for novel chemical classes of inhibitors with comparable predicted activity. The computer algorithm consults a library of ring systems and other molecular fragments of known structure and fits the most likely of these into the site, making chemical modifications where appropriate. The search has located diaminopteridines with calculated activity comparable to that of the best quinazolines for which the site was constructed. In addition, the search algorithm's unfettered imagination proposes much more bizarre candidates, such as a benzoxazoline‐2‐one dimer. Our present purpose is not to claim we have performed an exhaustive search for all possible antifolates, but rather to outline how the calculations are done and to demonstrate that these preliminary results are reasonable.
Rationalisations among Heterocyclic Partition Coefficients Part 2: The Azines
Authors: Lewis Susan J. , Mirrlees Margaret S. , Taylor Peter J. 
Published: October 2006

AbstractAzine π‐values are discussed in terms of Δπ, which is the difference in π‐value from that expected for benzene. It is shown that Δπ is close to zero for alkyl and most halogen groups, but for polar substituents capable of hydrogen bonding may be as high as ca. 1.6. Except for peri‐positions, these Δπ‐values may be correlated by a set of equations specific for different types of substituent position and containing terms which separately parameterise proton donor and acceptor ability. The rationale behind this treatment is justified in terms of the nature of the octanol‐water partitioning process and the manner in which electronic effects are expected to operate, in this context and that of the individual molecule. These equations will correlate those compounds for which they are expected to be applicable to Δ logP ± 0.12. Other topics discussed include: reasons for deviations among “irregular” substituents; the special problems of peri‐positions; multi‐substitution; and some consequences of this analysis for other types of compound.
Rational Selection of Test Series for QSAR‐Analysis
Authors: Schaper Klaus‐Jürgen 
Published: October 2006

AbstractA method for the rational selection of test series with low collinearities of molecular descriptors and high data variance is presented (RVS method). This method selects analogs on the basis of a selection criterium which combines multiple correlation coefficients R, relative parameter variances V and the synthetic feasibility S of test series. Special flexibility of the method is provided by weighting factors which are adapted until a satisfactory series is obtained. Examples of the application of the RVS method are given, and the results are compared with results from other selection techniques.
Computer‐Assisted Prediction of Bioactive Compounds Based on the Hansch‐Fujita Analysis
Authors: Takayama Chiyozo , Miyashita Yoshikatsu , Sasaki Shin‐Ichi , Yoshida Mototsugu 
Published: October 2006

AbstractComputer programs called PREHAC1 and PREHAC2, which aid in the impartial selection of substituents for the synthesis of highly bioactive compounds among congeners based on the Hansch‐Fujita analysis, were developed. The PREHAC1 and 2 programs are for aliphatic and aromatic monosubstituted derivatives and for aromatic disubstituted derivatives, respectively. Thirteen sets of physicochemical parameter values of 408 useful substituents were previously input into a data file as Master Data. PREHAC programs are activated by the input of the coefficients and intercept of the QSAR equation with the corresponding parameter codes, the information on the number of the substituents to be printed out, etc., and then Master Data is searched. Calculated activity values are ranked in descending order and the high‐ranking substituents are printed out according to the specified number. An example is presented to illustrate the programs.
Some Critical Remarks Concerning the Inductive Parameter σI Part II: Aliphatic Carboxylic Acids
Authors: Bijloo Greetje J. , Rekker Roelof F. 
Published: October 2006

AbstractCorrelation analysis was applied to pKa values of a series of 91 aliphatic carboxylic acids in order to obtain substantial evidence for a σI = 0.00 parametrization of alkyl groups. A very good correlation with r = 0.998 could be established. The results confirm our findings with aliphatic amines as discussed in a previous paper in this series. Some apparent anomalies in the pKa values of amino‐substituted carboxylic acids, diamines and dicarboxylic acids will be treated.
Nonadditivity of 1‐Octanol/Water Partition Coefficients of Disubstituted Benzenes: An Explanation and Its Consideration in Log P Estimation
Authors: Dunn W. J. , Johansson E. , Wold S. 
Published: October 2006

AbstractPartition coefficient data (logP) for 121 benzene derivatives from the 1‐octanol/water system were subjected to principal components analysis (PCA). The statistical analysis shows an interaction between substituents on a benzene nucleus that affects logP values in a measurable way. The interaction can be modelled by Hammet's ϕ, and is probably due to differences in solvent‐solute hydrogen bonding in the two phases, 1‐octanol and water. The significance of these results for the prediction of logP values is discussed.
Estimation of Substituent Group Electronic Influence from Molecular Connectivity Delta Values
Authors: Kier Lemont B. , Hall Lowell H. 
Published: October 2006

AbstractAn estimation of the relative electronegativities of atoms in their valence state is presented, based upon counts of valence and sigma electrons other than those bonding with hydrogen. This Kier/Hall valence state electronegativity is linearly related to the Mulliken‐Jaffe' electronegativity. This estimation is extended to include group electronegativities. Groups, treated as benzene ring substituents, are evaluated in terms of their electronic influence on a benzene ring. This influence is partitioned into electronegativity equalization effects through sigma and pi orbital interactions plus lone pair orbital pressure on the ring pi system. A simple summation of these three influences, calculated very easily from structure, is found to be well correlated with the Hammett values for 25 common substituents for both para and meta position values. The present treatment deals with first row elements.
Correlation and Estimation of Aqueous Solubilities of Polycyclic Aromatic Hydrocarbons
Authors: Baker Ronald J. , Acree William E. , Tsai Chun‐Che 
Published: October 2006

AbstractQuantitative structure‐activity relationships have been studied for the aqueous solubilities of 25 polycyclic hydrocarbons (PAH) at 25°C. Multiple regression correlations are reported between aqueous solubility (X) and molecular size descriptor (molecular surface area, molecular volume or molecular weight), melting point temperature (MP), and a newly‐defined molecular symmetry and structure descriptor (R · rd). A generalized correlation takes the form of log X = a0 + a1 (Molecular size descriptor) + a2 (MP‐25) + a3 R · rd in which ai refers to the ith regression coefficient, R is a molecular redundancy index and rd is the summation of interatomic distances in a molecule. These correlations enable the aqueous solubility to be estimated from melting point temperatures and structural information. The 3‐parameter expressions best predict the experimental solubilities and are superior to the 2‐parameter expressions (a3 = 0) suggested in the past. For the majority of compounds considered, agreement between observed and estimated solubility is quite good. The correlations may also be useful in screening experimental solubility data for which serious discrepancies exist in the literature.
Correlation Between Affinity Towards β‐Adrenergic Receptors and Electrostatic Potentials of Phenylethylamine Derivatives
Authors: Šolmajer Tomaž , Hodošček Milan , Hadži Dušan , Lukovits Istvan 
Published: October 2006

AbstractMolecular electrostatic potentials (MEP) were computed from ab‐initio wave functions for twelve 3,4‐substituent combinations which appear in 52 phenylethylamine derivatives active as ligands to β‐adrenergic receptors. The values of MEP (VA) at a defined point were used as independent variables in multiple regression analysis to derive equations connecting affinities and intrinsic activities of the ligands as determined by Bilezikian et al. [2]. The side chain potentials (VN) computed previously [1] were also used as independent variables. The significance of the electrostatic forces in determining both the affinities and the intrinsic activities is demonstrated.
Selective Antimetastatic Triazenes: A Quantitative Approach
Authors: Lassiani Lucia , Nisi Carlo , Giraldi Tullio , Sava Gianni , Cuman Riccardo 
Published: October 2006

AbstractQuantitative structure‐activity relationships have been formulated examining a series of para substituted phenyldimethyl‐triazenes for their differential effects on the subcutaneous growth of Lewis lung carcinoma and on the formation of its pulmonary metastases in mice. When the data were expressed as log 1/C, the QSAR obtained for toxicity as well as for the effects on primary tumor and metastases showed a similar dependency on the physicochemical constant chosen. Since drug potency expressed as log 1/C is obtained at the expenses of different toxicities for the tumor bearing host, drug activity was also expressed as the effect obtained at maximum tolerated drug dosages (log T/C). The QSAR resulting from the expression of the data as log T/C showed a dissociation between the effects on primary tumor as compared with those on metastases, quantitatively evidencing the observed selective antimetastatic properties of these substances. Aryldimethyltriazenes more active against metastases could be theoretically obtained for values of logP outside the range presently considered.
PCB and Dioxin Binding to Cytosol Receptors: A Theoretical Model Based on Molecular Parameters
Authors: McKinney J. D. , Long G. A. , Pedersen L. 
Published: October 2006

AbstractA model based on dispersion interactions is developed to interpret the cytosol‐PCB binding data of Bandiera et al. [1]. The essential parameters in the model are the PCB polarizability and the receptor to PCB separation distance. An approximate linear free energy relationship is derived in terms of these parameters. It is suggested that the oxygens in PCDDs may lead to stabilizing hydrogen bonding with the receptor; this reasonably accounts for the unusual binding affinity of certain PCDDs. Finally, a derivation of [EC50] for the PCBs displacement reaction based solely on equilibrium theory is shown to lead to an expression consistent with the experimental correlation if the displaced TCDD aggregates with the solution PCB or any other cytosol component.
Some Critical Remarks Concerning the Inductive Parameter σI Part IV: Parametrization of the Ortho Effect in Anilines and Pyridines
Authors: Bijloo Greetje J. , Rekker Roelof F. 
Published: October 2006

AbstractCorrelation analysis was applied to pKa values of a series of 70 anilines and a series of 44 pyridines in order to obtain more evidence for the correct rules of parametrization of ortho‐substituents as suggested by Fujita and Nishioka in 1976. The results confirm the findings reported in the third article in this series.For the inductive effect parameter σI ‐ used in this type of equations ‐ again a σI = 0.00 parametrization for alkyl groups is applied. The results are in agreement with the findings for aliphatic amines and aliphatic carboxylic acids as discussed in previous papers in this series.Good correlations with r = 0.9970 for anilines and r = 0.9926 for pyridines could be found.
Quantitative description of α2‐adrenergic potency in terms of receptor affinity and intrinsic activity
Authors: De Jonge Adriaan , Timmermans Pieter B. M. W. M. , van Zwieten Pieter A. 
Published: October 2006

AbstractAttempts were made to describe quantitatively peripheral as well as central α2‐adrenergic potency as a linear combination of affinity for and intrinsic activity at α2‐adrenoceptors within a series of 16 α‐adrenergic agonists, of the imidazolidine type. Central α2‐adrenergic potency was quantified as the ability of the compounds to decrease mean arterial pressure of pentobarbitone‐anaesthetized normotensive rats by 20% following intravenous administration. Peripheral α2‐adrenergic potency was measured in pithed normotensive rats as the inhibitory activity on stimulation‐induced tachycardia. Central and peripheral α2‐adrenergic potencies were linearly correlated upon including logP′ (octanol/buffer partition coefficient, pH 7.4, 37°C), showing the different accessibility of the two α2‐adrenoceptor populations. Affinity of the imidazolidines for α2‐adrenoceptors was determined by the displacement of 3H‐clonidine from its specific binding sites in membranes from rat brain. The linear relationships between peripheral and central α2‐adrenergic potency on the one hand and affinity for α2‐adrenoceptors with or without the addition of logP′ on the other hand were significantly improved by incorporation of a term standing for receptor activation, i.e. intrinsic activity at α2‐adrenoceptors. The results support current concepts in receptor theory stating that only when both efficacy and affinity are known, can the activity of the agonist be predicted with reasonable certainty.
The Chemical Shift of the Alpha Carbon in Amino‐Acids as a Parameter for QSAR Studies of Oligopeptides
Authors: Fauchère Jean‐Luc , Lauterwein Jürgen 
Published: October 2006

AbstractThe 13C‐NMR chemical shift δH of the α‐carbon in amino‐acids is proposed as a new parameter for QSAR studies of biologically active oligopeptides. δH which is known for common amino‐acids, is mainly a measure of the electronic shielding of the α‐carbon. In the aliphatic series, it is computable by empirical rules and very sensitive to β‐branching.In this study, δH is shown to describe accurately as a single continuous parameter the variations of the biological activity of angiotensin II, when the residue in its position 5 is varied.
Quantitative Structure‐Activity Relationships in the Displacement of the Dihydrosafrole Metabolite‐Cytochrome P‐450 Complex
Authors: Murray Michael , Marcus Craig B. , Wilkinson Christopher F. 
Published: October 2006

AbstractTwenty‐one 2‐substituted benzimidazoles and two naphtho‐[2,3‐d]‐imidazoles were evaluated for their in vitro ability to displace the dihydrosafrole metabolite from its complex with microsomal cytochrome P‐450. Several proved to be extremely effective displacers, the most active being 2‐(2′,3′‐dichloro‐phenoxy)methylbenzimidazole. Quantitative structure‐activity analyses (QSAR) using the descriptors log P (partition coefficient) and MR2 (molar refractivity) established that up to eighty‐eight percent of the variance in the displacement data could be accounted for in terms of the MR2 of the 2‐substituent of the benzimidazole ring. Other QSAR analyses involving molecular connectivity indices (χ) supported the assertion that steric parameters are of primary importance in the displacement process.
Hansch Approach and Kinetics of Drug Activities
Authors: Baláž Štefan , Šturdík Ernest , Tichý Miloň 
Published: October 2006

AbstractThe relations between isotoxic concentration, the disposition function (the latter relating the concentration of a drug in the receptor region to the initial external concentration) as well as equilibrium and rate characteristics of the drug‐receptor interaction are derived using mass action law for three types of the drug‐receptor interactions (noncovalent interaction, covalent bond, noncovalent interaction followed by covalent bond formation). The results are shown to be consistent with the Hansch equation in most cases, exceptions being discussed.
Shape Indexes of Orders One and Three from Molecular Graphs
Authors: Kier Lemont B. 
Published: October 2006

AbstractThe concept of a shape index derived from the molecular graph previously described, has been expanded to include two additional indexes derived from counts of one‐path and three‐path fragments. Algorithms have been derived using the original model of defining two limiting structures and quantitating any intermediate structural shape relative to these two. Counts of one‐path fragments and three‐path fragments lead to shape indexes of 1K and 3K. The information encoded in each has been extracted in terms of shape attributes. The concept that molecular shape can be viewed as a sum of isolated attributes is put forward and a partial series is presented based on the indexes developed to date. Several examples of QSAR applications are presented where two of these shape indexes are revealed to encode enough information to give good correlations.
A Comparison of Some Measures for the Determination of Inter‐Molecular Structural Similarity Measures of Inter‐Molecular Structural Similarity
Authors: Willett Peter , Winterman Vivienne 
Published: October 2006

AbstractSix weighting schemes and six similarity coefficients have been used in a systematic comparison of measures for the determination of inter‐molecular structural similarity. The effectiveness of the measures for molecular property prediction was tested using sixteen small sets of compounds for which property data was available. The comparison suggests that the weighting of fragments by their frequency of occurrence in molecules is often useful, but that there are only small differences in performance between the similarity coefficients tested.
Comparison Between X‐Ray Crystallographic Data and Physicochemical Parameters with Respect to Their Information about the Calcium Channel Antagonist Activity of 4‐Phenyl‐1,4‐dihydropyridines
Authors: Berntsson Peder , Wold Svante 
Published: October 2006

AbstractTriggle et al. [1] investigated a number of 4‐phenyl‐1,4‐dihydropyridines with respect to their X‐ray structure and the relation between a selection of six X‐ray variables and the calcium channel antagonist activity. We here extend their structure‐activity relation to include all fourteen X‐ray data given in ref. [1]. In addition, we develop an alternative QSAR based on a conventional physicochemical parametrization of the phenyl ring.A PLS model based on the physicochemical data separates active from inactive compounds, in contrast to the model based on the X‐ray data. Both PLS models with physicochemical data and with X‐ray data adequately predict the quantitative variation in activity for the active compounds.
QSAR of 1,4‐Naphthoquinones as Inhibitors of Photosystem II Electron Transport
Authors: Oettmeier Walter , Dierig Christoph , Masson Klaus 
Published: October 2006

Abstract42 1,4‐naphthoquinones with substituents in the 2‐ and 3‐position were examined for their inhibitory activity on photosynthetic electron transport through photosystem II. The best ones were active in concentrations in the μM range or less. A QSAR was established, using the sum of the σ‐Hammett parameters and Taft's steric E parameter for the substituents in the 2‐ and 3‐position. The QSAR could be improved, if instead of the E, the STERIMOL parameters L (for the 2‐position) and B3 and B4 (for the 3‐position) were applied. QSAR for different types of photosystem I1 inhibitors (urea, phenolic, quinoid) were compared. The differences in between them do support the idea of nonidentical though possibly overlapping binding sites at the reaction center complex of photosystem II.
Polychlorinated Dibenzofuran (PCDF) Binding to the Ah Receptor(s) and Associated Enzyme Induction. Theoretical Model Based on Molecular Parameters
Authors: Long G. , McKinney J. , Pedersen L. 
Published: October 2006

AbstractA model based on dispersion interactions previously developed to interpret cytosol receptor (Ah receptor)‐PCB binding data is applied to PCDFs and extended to interpret associated monooxygenase induction potencies (AHH and EROD activities). The essential parameters in the model are the PCDF polarizability and the PCDF to receptor separation distance. An empirical relationship based on solvent accessible polar surface area is used to estimate the solvation contribution to the binding free energy. Considerations of PCDF solubility and desolvation energy in the assay are suggested as possible refinements of the model which may improve predictive ability. PCDF binding and enzyme induction potencies are seen to increase with increasing polarizability which is controlled to a large extent by the number of chlorine substituents.
Effect of Substituents at Position 2 on the 1H NMR Chemical Shift of Protons of 2‐Methylbenzimidazole Derivatives
Authors: Nasal Antoni , Kaliszan Roman , Kuźmierkiewicz Wojciech 
Published: October 2006

AbstractFor a series of 17 newly synthesized 2‐methylbenzimidazole derivatives a significant correlation was found between the 1H NMR chemical shift (in ppm) of hydrogens at position 2 and the sum of the inductive electronic constants of the substituents attached to this position. The substituent attached to the nitrogen atom of the imidazole moiety has a significantly less pronounced effect on the substituent in 2‐position hydrogen chemical shift.
A Molecular Modeling Based upon an X‐Ray Crystal Structure: The Enzyme‐Ligand Complexes between Porcine Pancreatic Elastase and Acetyl‐Alanine‐Alanine(Glycine)‐Alanine
Authors: Fujita Tadao 
Published: October 2006

AbstractMolecular models of the complexes between porcine pancreatic elastase (PPE, EC 3.4.4.7), and acetyl‐alanine‐alanine‐alanine (AAA) and acetyl‐alanine‐glycine‐alanine (AGA) are constructed by means of molecular mechanics (MM) calculation, based upon the previously reported X‐ray structure between PPE and acetyl‐alanine‐proline‐alanine (APA). The MM calculations have been carried out in a 12 Å scoop region from the alpha carbon atom of the second residue of the ligand. During the energy minimization, bond distance, bond angles, improper dihedral angles and dihedral angles are relaxed without a constrain. The resulting structures suggested that the ligands, AAA and AGA could be bound to the active site of PPE in the similar binding arrangements which had been shown in the X‐ray structure between PPE and APA. The stronger inhibition of APA in vivo may be caused by the structural stability to enzymatic hydrolysis.