Lipinski

An extensive series of studies for the prediction of aqueous solubility has been reported in the literature, as summarized by Lipinski et al. [15] and jorgensen and Duffy [16]. These methods can be categorized into three types 1 correlation of solubility with experimentally determined physicochemical properties such as melting point and molecular volume 2) estimation of solubility by group contribution methods and 3) correlation of solubility with descriptors derived from the molecular structure by computational methods. The third approach has been proven to be particularly successful for the prediction of solubility because it does not need experimental descriptors and can therefore be applied to collections of virtual compounds also. 

To become familiar with Lipinski s Rule of Five"... 

In general, the first step in virtual screening is the filtering by the application of Lipinski s Rule of Five [20]. Lipinski s work was based on the results of profiling the calculated physical property data in a set of 2245 compounds chosen from the World Drug Index. Polymers, peptides, quaternary ammonium, and phosphates were removed from this data set. Statistical analysis of this data set showed that approximately 90% of the remaining compounds had ... 

The property calculation experiment offers a list of 34 molecular properties, including thermodynamic, electrostatic, graph theory, geometric properties, and Lipinski properties. These properties are useful for traditional QSAR activity prediction. Some are computed with MOPAC others are displayed in the browser without units. A table of computed properties can be exported to a Microsoft Excel spreadsheet. 

The basic principle of e-beam SNMS as introduced by Lipinsky et al. in 1985 [3.60] is simple (Fig. 3.30) - as in SIMS, the sample is sputtered with a focused keV ion beam. SN post-ionization is accomplished by use of an e-beam accelerated between a filament and an anode. The applied electron energy Fe a 50 20 eV is higher than the range of first ionization potentials (IP) of the elements (4—24 eV, see Fig. 3.31). Typical probabilities of ionization are in the 0.01% range. SD and residual gas suppression is achieved with electrostatic lenses before SN post-ionization and energy filtering, respectively. 

Lactic acid and levulinic acid are two key intermediates prepared from carbohydrates [7]. Lipinsky [7] compared the properties of the lactide copolymers [130] obtained from lactic acid with those of polystyrene and polyvinyl chloride (see Scheme 4 and Table 5) and showed that the lactide polymer can effectively replace the synthetics if the cost of production of lactic acid is made viable. Poly(lactic acid) and poly(l-lactide) have been shown to be good candidates for biodegradeable biomaterials. Tsuji [131] and Kaspercejk [132] have recently reported studies concerning their microstructure and morphology. 

Lipinski, C., Lombardo, F., Dominy, B., and Feeney, P. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 23 3—25. 

Lipinski, C. A. (2000). Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Tox. Meth. 44 235-249. 

In both variants of the approach, i) and ii), the ligands detected in a NMR screen would be subjected to further modifications, and become larger during the design process. The properties of the compound library need to fulfill therefore a number of NMR-specific requirements. The compounds need to be soluble in water, their molecular properties should not exceed half the number that is defined in the Lipinski rules for molecular... 

Lipinski C, Hopkins A. Navigating chemical space for biology and medicine. Nature 2004 432 855-61. 

Lipinski CA. Drug-like properties and the causes of poor solubility and poor... 

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