title: Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat.
abstract: The relationship of rotatable bond count (N(rot)) and polar surface area (PSA) with oral bioavailability in rats was examined for 434 Pharmacia compounds and compared with an earlier report from Veber et al. (J. Med. Chem. 2002, 45, 2615). N(rot) and PSA were calculated with QikProp or Cerius2. The resulting correlations depended on the calculation method and the therapeutic class within the data superset. These results underscore that such generalizations must be used with caution.
authors.affiliation: Computational Chemistry and Nonclinical Statistics and CNS Drug Metabolism, Pfizer Global R&D, Groton Laboratories, Eastern Point Road, 8200-36, Groton, Connecticut 06340, USA.
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Lu
authors.forename: Kimberly
authors.initials: K
authors.lastname: Crimin
authors.forename: Jay T
authors.initials: JT
authors.lastname: Goodwin
authors.forename: Patrizia
authors.initials: P
authors.lastname: Crivori
authors.forename: Christian
authors.initials: C
authors.lastname: Orrenius
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tandler
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Vidmar
authors.forename: Benny M
authors.initials: BM
authors.lastname: Amore
authors.forename: Alan G E
authors.initials: AG
authors.lastname: Wilson
authors.forename: Pieter F W
authors.initials: PF
authors.lastname: Stouten
authors.forename: Philip S
authors.initials: PS
authors.lastname: Burton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations