Physiochemical drug properties associated with in vivo toxicological outcomes

被引：699

作者：

Hughes, Jason D. ^{[1
]}

Blagg, Julian ^{[2
]}

Price, David A. ^{[3
]}

Bailey, Simon ^{[4
]}

DeCrescenzo, Gary A. ^{[5
]}

Devraj, Rajesh V. ^{[5
]}

Ellsworth, Edmund ^{[6
]}

Fobian, Yvette M. ^{[5
]}

Gibbs, Michael E. ^{[3
]}

Gilles, Richard W. ^{[5
]}

Greene, Nigel ^{[3
]}

Huang, Enoch ^{[1
]}

Krieger-Burke, Teresa ^{[6
]}

Loesel, Jens ^{[7
]}

Wager, Travis ^{[3
]}

Whiteley, Larry ^{[5
]}

Zhang, Yao ^{[3
]}

机构：

[1] Pfizer Res Technol Ctr, Cambridge, MA 02139 USA

[2] Inst Canc Res, Haddow Labs, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England

[3] Pfizer Inc, Groton, CT 06340 USA

[4] Pfizer, San Diego, CA 92121 USA

[5] Pfizer, St Louis, MO 63017 USA

[6] Pfizer, Ann Arbor, MI 48105 USA

[7] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 17期

关键词：

toxicity; polar surface area; ClogP; adverse events;

D O I：

10.1016/j.bmcl.2008.07.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Relationships between physicochemical drug properties and toxicity were inferred from a data set consisting of animal in vivo toleration (IVT) studies on 245 preclinical Pfizer compounds; an increased likelihood of toxic events was found for less polar, more lipophilic compounds. This trend held across a wide range of types of toxicity and across a broad swath of chemical space. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4872 / 4875

页数：4

共 16 条

[1]

Azzaoui K, 2007, CHEMMEDCHEM, V2, P874, DOI 10.1002/cmdc.200700036

[2] Structure-activity relationships for In vitro and In vivo toxicity [J].