Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat

被引：140

作者：

Lu, JJ

Crimin, K

Goodwin, JT

Crivori, P

Orrenius, C

Xing, L

Tandler, PJ

Vidmar, TJ

Amore, BM

Wilson, AGE

Stouten, PFW

Burton, PS

机构：

[1] ADMETRx Inc, Kalamazoo, MI 49008 USA

[2] Pfizer Global R&D, Groton Labs, Computat Chem & Nonclin Stat, Groton, CT 06340 USA

[3] Pfizer Global R&D, Groton Labs, CNS Drug Metab, Groton, CT 06340 USA

[4] Nerviano Med Sci, Attrit Reducing Technol & Computat Sci, I-20014 Nerviano, MI, Italy

[5] Pfizer Global Res & Dev, Computat Chem, St Louis, MO 63017 USA

[6] Pfizer, Midwest Nonclin Stat, Kalamazoo, MI 49007 USA

[7] Lexicon Genet, The Woodlands, TX 77381 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 24期

关键词：

D O I：

10.1021/jm0306529

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：6104 / 6107

页数：4

共 12 条

[1] Application of hydrogen bonding calculations in property based drug design [J].