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Biomedical subjects

L B Kier

Publications and source records attributed to L B Kier.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1976

Molecular connectivity VII: specific treatment of heteroatoms.

The molecular connective index, chi, initially designed for hydrocarbons, has been formally extended to molecules containing heteroatoms. The sigma value of the heteroatom is modified to take account of its number of attached hydrogen atoma, sigmaiv = Zv - hi. These values were successfully tested on boiling points and molar refractions. A table of sigmav values is presented for nitrogen, oxygen, fluorine, chlorine, bromine, and iodine in various bonding situations.

Chemical Phenomena↗
PubMed1976

Molecular connectivity. 6. Examination of the parabolic relationship between molecular connectivity and biological activity.

The topologically derived, nonempirical molecular connectivity index, chi, for several classes of compounds is shown to be parabolically related to the biological activities of these compounds. Similar nonlinear relationships were previously shown between the octanol-water partition coefficients, expressed as log P, of the compounds and their biological activities. These and previous studies indicate that many physiochemical properties presently used in structure-activity studies may be intermediaries between the nonempirical molecular structure encoded in chi and measured biological activities.

Amines↗
PubMed1975

Nature of anionic or alpha-site of cholinesterase.

The nature of the so-called anionic binding site of acetylcholinesterase was investigated using a technique called receptor mapping using model interaction calculations. The results support the suggestion that coulombic forces play only a minor role in the binding event at this enzyme site.

Acetylcholine↗
PubMed1975

Molecular connectivity. I: Relationship to nonspecific local anesthesia.

A very significant linear correlation was found between a recently proposed connectivity index and molecular polarizability, cavity surface areas calculated for water solubility of alcohols and hydrocarbons, and biological potencies of nonspecific local anesthetics. The simplicity of calculation of the index from the connectivity in the molecular skeleton, together with the very significant correlation, indicates its practical value.

Anesthetics, Local↗