Topological PSA

Ertl and co-workers [20] have developed such a method for generating a topological PSA (TPSA) based on 3D PSA values for 43 fragments resulting from an analysis of 34,810 compounds taken from the WDI database. The correlation between PSA and TPSA is very high (r2 = 0.982). 

Fig. 15.18 Selected examples of the distribution of predicted PSA scores for diversity reagents within a 2400-member library built around a common core. Topological PSA scores were calculated according to the method published by ErtI and expressed in A. Significant number of predicted scores greater than 140 is sufficient criteria for deselection of that diversity reagent.

Palm et al. [3] took into account the flexibility of molecules by using molecular mechanics to calculate an averaged PSA according to a Boltzmann distribution. Later Clark [4,5] found that the use of a representative conformation was sufficient for the calculation of reliable PSA values. Ertl [6] developed a method to calculate PSA as the sum of fragment contributions and proposed a topological PSA (TPSA). The advantage of TPSA is that it can be directly calculated from the 2D chemical structure, which makes the calculation rapid and reproducible. 

D structure and use molecular topology instead (topological PSA, or TPSA). Using these algorithms, a PSA filter can be applied to large collections of real or virtual compounds to eliminate the ones with high PSA. 

This picture of a fresh particle coating shows the characteristic topology of the PSA. 

Fig. 19. Topology and peel removal of discrete PSA particles from a substrate.

Votano et al., Molecular Diversity, 2004 [27] New predictors for several ADME/Tox properties aqueous solubility, human oral absorption, and Ames geno-toxicity using topological descriptors 612 ANN 16% (ra= 195) Clog P, PSA, and topological descriptors (n= 10)... 

Rotatable bond count (RotB) rotatableBondCount() Stereocenter count (nStereo) chiralCenterCount() Topological polar surface area (tPSA) PSA()... 

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