Influence of Molecular Flexibility and Polar Surface Area Metrics on Oral Bioavailability in the Rat
- 23 October 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 47 (24) , 6104-6107
- https://doi.org/10.1021/jm0306529
Abstract
The relationship of rotatable bond count (Nrot) 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). Nrot 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.Keywords
This publication has 10 references indexed in Scilit:
- A Comparison of Physiochemical Property Profiles of Development and Marketed Oral DrugsJournal of Medicinal Chemistry, 2003
- Classification Structure-Activity Relations (C-SAR) in Prediction of Human Intestinal AbsorptionJournal of Pharmaceutical Sciences, 2003
- Selection criteria for drug‐like compoundsMedicinal Research Reviews, 2003
- Nonleadlikeness and leadlikeness in biochemical screeningDrug Discovery Today, 2003
- Application of hydrogen bonding calculations in property based drug designDrug Discovery Today, 2002
- Molecular Properties That Influence the Oral Bioavailability of Drug CandidatesJournal of Medicinal Chemistry, 2002
- Predicting Drug Absorption: How Nature Made It a Difficult ProblemThe Journal of Pharmacology and Experimental Therapeutics, 2002
- Crystalline solidsAdvanced Drug Delivery Reviews, 2001
- Ritonavir: An Extraordinary Example of Conformational PolymorphismPharmaceutical Research, 2001
- Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport PropertiesJournal of Medicinal Chemistry, 2000