Comparative molecular field analysis of some clodronic acid esters

Abstract

Comparative molecular field analysis (CoMFA) has been used as a three-dimensional quantitative structure-activity relationship (QSAR) method to correlate three different types of biological activity data with physicochemical properties of some clodronate ester analogues, which act as bone-resorption regulators in cell cultures and rats. The QSAR studies show the importance of the steric properties of these new bisphosphonate derivatives for the inhibition of bone resorption in bone cell cultures and for their bioavailability in rats. This information will be used in predicting the structure of new more potent bisphosphonic compounds.

Use of the hydrogen bond potential function in a comparative molecular field analysis (CoMFA) on a set of benzodiazepines

“…These energies are measured as interactions between each ligand and properly selected probe through simple functions of molecular mechanics force fields. CoMFA has been employed not only in pharmacodynamic studies [8][9][10][11][12] but also to model chemical equilibrium constants and traditional Q SAR descriptors [13][14][15]. The most predictive model is chosen from cross-validation procedures [6,7].…”

Bisphosphonate Prodrugs

“…[20][21][22] The accurate log P app for any BP is difficult to measure, due to very low lipophilicity, for examples, an estimated value for clodronate is extremely low ca. -6 [23]. Obviously, higher log P app values can be achieved if one or more ionizable groups are masked with bioreversible functional groups.…”

Hydrogen-bonding effects, electrostatic potential, and the antitumor activity of flavone acetic acid and related compounds. II. Ab initio studies on the second stable conformations

“…Mezey and coworkers [161 developed a topological approach to assess molecular similarity. Cramer et al [17] introduced the so-called comparative molecular field analysis (CoMFA) method, which uses partial least-square statistics to analyze the steric and electrostatic field lattices of drug molecules and is now widely used [18][19][20][21]. Another molecular similarity index, R,,, due to Carbo et al [22,231, is determined from some properties PA and P, of the two molecules as Obviously, R A B represents the similarity of the shapes of the P property distributions but not of the magnitudes as well, because the substitution of PA = UP, into Eq.…”