title: Use of 3D properties to characterize beyond rule-of-5 property space for passive permeation.
abstract: The application of conformationally dependent measures of size and polarity to characterize beyond rule-of-5 (Ro5) space for passive permeation was investigated. Specifically, radius of gyration, an alternative to molecular weight, and three-dimensional polar surface area and the generalized Born/surface area dehydration free energy, alternatives to hydrogen-bond donor and acceptor counts, were computed on models of the permeating conformations of over 35 000 molecules. The resulting guidelines for size and polarity, described by the 3D properties, should aid the design of Ro5 violators with passive permeability.
authors.forename: Cristiano R W
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mathiowetz
authors.forename: Marina
authors.initials: M
authors.lastname: Shalaeva
authors.forename: Gilles
authors.initials: G
authors.lastname: Goetz
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004285:Dogs; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D061985:Madin Darby Canine Kidney Cells; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D008970:Molecular Weight; D055553:Prescription Drugs / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D055553:Prescription Drugs