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Biomedical subjects

Y C Martin

Publications and source records attributed to Y C Martin.

6 recordsLinked to original sources
PubMed1991

Direct prediction of dissociation constants (pKa's) of clonidine-like imidazolines, 2-substituted imidazoles, and 1-methyl-2-substituted-imidazoles from 3D structures using a comparative molecular field analysis (CoMFA) approach.

The applicability of a comparative molecular field analysis (CoMFA) method to reproduce and predict the pKa values of 28 clonidine-like imidazoline analogues and 16 2-substituted imidazoles has been investigated with the GRID force field. Molecular fields calculated with an H+ probe and AM1 partial atomic charges produced a correlation with a small standard deviation and a high correlation coefficient with cross validation. It was concluded that the CoMFA treatment of electrostatic effects is suitable for predicting pKa values and thus for the examination of the electronic effects in 3D quantitative structure-activity relationships.

Clonidine↗
PubMed1976

Theoretical model-based equations for the linear free energy relationships of the biological activity of ionizable substances. 1. Equilibrium-controlled potency.

Because of the ambiguities of how to treat ionization in empirical equations which relate biological activity to partition coefficient by use of a (log P)2 term, a theoretical approach to the problem is proposed. Based on a simplified view of assays of potency following in vitro or continuous infusion administration of drugs, equations have been derived from a combination of mass law, equilibrium, and extrathermodynamic assumptions. In general form the equations which relate potency to partition coefficient (P) and degree of ionization (alpha) are the following. If the neutral form reacts with the receptor, log (1/C) =-log [1 + SIGMAM(DIPci) + sigman[aj/Pb(1-alpha4y]] + X. If the ionic form reacts with the receptor, log (1/C) =-log [1 + (1 - Alphan)/(alphan)[sigmam(diPci) + sigman[aj/Pb(1-alphaj)]]] + X. In this generalized model there are m nonaqueous compartments and n aqueous compartments of different pH. The parameters a, b, c, and d can be interpreted in terms of the model. The shape of the log (1/C) vs. log P curve may be asymptotic, linear, or composed of two portions of unequal slope which meet at an optimum or a bend. With the use of these equations it is possible to examine whether the ion or the neutral form is the active species and whether there is hydrophobic bonding to the receptor and/or an inert compartment. The models may be further extended to include terms other than log P and alpha.

Chemical Phenomena↗
PubMed1975

Regression analysis of the relationship between physical properties and the in vitro inhibition of monoamine oxidase by propynylamines.

Regression analysis of the potency of inhibition of monoamine oxidase by 47 propynylamines revealed that there are three determinants of inhibitory potency: (1) the smallest substituent on the nitrogen must be methyl or hydrogen in order for any activity to be observed; (2) potency is parabolically related to pKa-the optimum pKa is 6.2; and (3) ortho-substituted benzylamine analogs are ten times more potent than predicted on the basis of pKa values. The optimum pKa cannot be explained by differences in fraction ionized but rather in terms of the multistep sequence whereby these compounds inhibit MAO. A very slight positive effect of hydrophobicity on potency was found. The potency of several analogs not included in the original analysis was predicted.

Alkynes↗