Isopropionic acid

Abbreviations AA acetic acid derivative, IPA isopropionic acid derivative, BA benzoic acid... 

Due to their low rate of covalent binding to protein, it might be suggested that compounds bearing benzoic acid or isopropionic acid substituents at the a-carbon of the carboxylic acid moiety should be considered when designing new chemical entities, provided these functional groups do not undermine desirable pharmacological activity. 

Figure 15.5 shows a hypothetical model PLS model for a set of compounds. The analysis shows that the cell-based lunclional assays (isopropionic acid) (IPA)-rat, IPA-human, and bioassay) do not correlate well with the receptorbinding assay. On the other hand, the cell-based assays are correlated well with the pharmaceutical properties, such as solubility and permeability. The model shows that increased MW and hydrogen-bonding capacity will improve potency. That, however, will decrease solubility and permeability and make them less druglike. So, for this series of compounds, it is important to find a balance between potency and druglike properties. 

To further our understanding of interaction between the heme isopropionate side chains and the solvent, the kinetic energy relaxation of the excited heme in Mb was simulated in various solvents, including normal water (HjO), heavy water (D2O), normal glycerol (Gly-hg), deuterated glycerol (Gly-dg), and a nonpolar solvent. Two forms of the heme, one native and one lacking acidic side chains, were employed in the simulations which, together with different solvents, provided various interaction feature between the heme and the environment [55]. 

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