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Biomedical subjects

L B Kier

Publications and source records attributed to L B Kier.

At least 19 recordsLinked to original sources
PubMed1992

A quantitative structure-activity relationship (QSAR) study of alkylpyrazine odor modalities.

The odor strength of a series of alkylpyrazines has been quantitatively investigated applying molecular connectivity, molecular shape, and the recently developed electrotopological state indices. The successful use of the latter parameters indicates that both electronic and topological features contribute to the odor strength of the compounds under study, while the specific role of the two nitrogen atoms is revealed.

Chemical Phenomena↗
PubMed1991

The concept of molecular structure in structure-activity relationship studies and drug design.

We can justify the use of any model, method, or algorithm if we clearly state our goals, understand the basis of our procedures, and fully appreciate the true nature and limitations of the results. As we have illustrated here, the creation of new wisdom may appear to be a consequence of our labors. There are cases, however, where this creation may be only an illusion. In any analysis of structure-activity, property-activity, or structure-property relationships, the degree of understanding of the nature of the starting data therefore determines the level of confidence ascribable to any result and prediction. This is, in essence, the message of our inquisitive meditations on the deep nature of structure-activity relationships.

Chemistry, Pharmaceutical↗
PubMed1990

An electrotopological-state index for atoms in molecules.

A new method for molecular structure description is presented in which both electronic and topological characteristics are combined. The method makes use of the hydrogen-suppressed graph to represent the structure. The focus of the method is on the individual atoms and hydride groups of the molecular skeleton. An intrinsic atom value is assigned to each atom as I = (delta v + 1)/delta, in which delta v and delta are the counts of valence and sigma electrons of atoms associated with the molecular skeleton. The electrotopological-state value, Si, for skeletal atom i is defined as Si = Ii + delta Ii, for second row atoms, where the influence of atom j on atom i, delta Ii, is given as sigma(Ii-Ij)/rij2; rij is the graph separation between atom i and atom j, counted as the number of atoms. The characteristics of the electrotopological state values are indicated by examples of various types of organic structures, including chain lengthening, branching, heteroatoms, and unsaturation. The relation of the E-state value to NMR chemical shift is investigated for a series of alkyl ethers. The E-state oxygen value gives an excellent correlation with the 17O NMR: r = 0.993 for 10 ethers. A biological application of the E-state values in QSAR analysis is given for the binding of barbiturates to beta-cyclodextrin.

Barbiturates↗
PubMed1979

Molecular connectivity study of halocarbon anesthetics.

The structure--activity relationships of 45 halogenated hydrocarbons using molecular connectivity were studied. A very good correlation was obtained between the anesthetic activity and the molecular connectivity term o chi v in addition to the polar hydrogen factor, QH. The equation reported accounts for the quantifies the known structure--activity observations on general anesthetics. The results are discussed briefly with reference to the mechanisms of action of general anesthetics.

Anesthetics↗
PubMed1979

Molecular connectivity analysis of hallucinogenic mescaline analogs.

The hallucinogenic (psychotomimetic) potency of 10 mescaline analogs was examined by molecular connectivity analysis. Potencies could be described by a two-term relating equation, which explained 94% of the variance in activity, on the basis of structural variation, 2,5-Dimethoxy substitution as well as the nature of the 4-position substituent played an important role in determining hallucinogenic potency. With the relating equation, reasonable potency predictions were made for six compounds not included in the initial investigation.

Hallucinogens↗
PubMed1978

Molecular connectivity study of muscarinic receptor affinity of acetylcholine antagonists.

A correlation between three molecular connectivity indexes and the muscarinic receptor affinity of 104 acetylcholine antagonists was found. Analysis of structure from these indexes reveals not only the importance of the onium and the bulky portions of the molecule but also their virtual independence of each other on the affinity. Analysis of the onium group portion of the molecules indicates that its contribution to the experimental affinity is virtually constant through a variety of structural variations. The influence of the bulky side chains, in contrast, is quite structure dependent. The equation relating connectivity indexes to muscarinic affinity of antagonists is capable of predicting the affinity of other antagonists as well as a number of agonist molecules.

Acetylcholine↗
PubMed1978

Molecular connectivity and substructure analysis.

Antimicrobial and antiviral data sets were analyzed by molecular connectivity. Standard structure--activity relationship equations of high quality were produced in both cases. For phenyl propyl ether activity against Staphylococcus aureus, the three variables 1chi, 3chiP, and 4chiUPC yielded an r of 0.957, significantly better than a pi,sigma analysis. Analysis of benzimidazole antiviral data (Lee strain, B flu virus) revealed that the one variable, 6chiP, yielded an r of 0.950, also better than a reported Hansch analysis. Both data sets were further analyzed by partitioning the important regression variables into terms representing various structural features of the molecules. For the phenyl propyl ethers, the para-region of the phenyl ring is important for improved activity and the negative coefficient on 3chiP corresponds to decreased activity for vic-dihydroxy compounds. For the alkylbenzimidazoles, substitution on the five-membered ring is highly important. No discrimination of six-membered ring positions was revealed. These structure--activity relationship observations can form the basis for synthetic decisions to improve activity.

Antifungal Agents↗
PubMed1977

Structure-activity studies using valence molecular connectivity.

The extension of the molecular connectivity concept to the treatment of heteroatom molecules affords an opportunity to examine structure-activity relationships in a wide variety of molecule series that possess biological activity. Four series are described in this report. The correlations found indicate that molecular connectivity is an extremely useful descriptor of structure in studying drug molecule structure-activity relationships.

Aniline Compounds↗
PubMed1977

Structure-activity studies on hallucinogenic amphetamines using molecular connectivity.

A series of ring-substituted hallucinogenic amphetamines has been analyzed using molecular connectivity. A correlating equation has been found between potency and connectivity terms. The equation permits an interpretation of SAR. The equation is capable of predicting potency for amphetamines not in the list and mescalines and tryptamines.

Amphetamines↗
PubMed1976

Molecular connectivity V: connectivity series concept applied to density.

The concept of the expanded series of the connectivity index, chi, is introduced and applied to a consideration of the density of three classes of molecules. Correlations are found using two terms in the expanded series. A preliminary reflection on the extended series terms is made. It is noted that the regression equation constant in the three studies is close to the phase volume, 0.7402, and the possible significance of this fact is discussed.

Alcohols↗