title: Rapid estimation of hydrophobicity for virtual combinatorial library analysis.
abstract: Novel NPH (Nonpolar, Polar, Hydrogen) descriptors for rapid estimation of hydrophobicity, amenable for filtering extremely large virtual combinatorial libraries (VCL) are proposed, based on atom counts: P_at, the sum of polar atoms (sum of oxygen, nitrogen, phosphorus and sulfur); NP_at, the sum of non-polar atoms (the sum of carbons and halogens minus P_at); SHDA (the sum of hydrogen bond donors and acceptors). In combination with molecular weight, the following related parameters are defined: MWP_at (the "polar" molecular weight); MWNP_at (the "nonpolar" molecular weight); and MWSHDA (the "hydrogen bonding" molecular weight). The NPH descriptors provide moderate-to-good predictive PLS models when external prediction is evaluated against measured logP values (q2 pred > 0.5, n = 7954) or against calculated logP values (q2 pred > 0.6, n = 18 991). Related to hydrophobicity, the NPH descriptors are intended for fast analyses of extremely large VCLs (10(6)-10(12) compounds), even before the enumeration of reactants into products occurs.
authors.affiliation: AstraZeneca R&D Mölndal, S-43183 Mölndal, Sweden. tudor.oprea@astrazeneca.com
authors.forename: T I
authors.initials: TI
authors.lastname: Oprea
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D005544:Forecasting; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008970:Molecular Weight; D013329:Structure-Activity Relationship