Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat.
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.
Lu
Jing J
JJ
Computational Chemistry and Nonclinical Statistics and CNS Drug Metabolism, Pfizer Global R&D, Groton Laboratories, Eastern Point Road, 8200-36, Groton, Connecticut 06340, USA.
Crimin
Kimberly
K
Goodwin
Jay T
JT
Crivori
Patrizia
P
Orrenius
Christian
C
Xing
Li
L
Tandler
Peter J
PJ
Vidmar
Thomas J
TJ
Amore
Benny M
BM
Wilson
Alan G E
AG
Stouten
Pieter F W
PF
Burton
Philip S
PS
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
D004364:Pharmaceutical Preparations