Using the Golden Triangle to optimize clearance and oral absorption

被引：283

作者：

Johnson, Ted W. ^{[1
]}

Dress, Klaus R. ^{[1
]}

Edwards, Martin ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, La Jolla, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 19期

关键词：

Oral absorption; Permeability; Efficiency; log D; Molecular weight; Molecular properties; Molecular descriptors; Clearance; Lipophilicity; Ligand efficiency; Ligand-lipophilicity efficiency; Golden triangle; Metabolism-lipophilicity efficiency; DRUG DISCOVERY; LOG-P; LIPOPHILICITY; PERMEABILITY; MONOLAYERS; EFFICIENCY; TRANSPORT; HPLC;

D O I：

10.1016/j.bmcl.2009.08.045

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The Golden Triangle is a visualization tool developed from in vitro permeability, in vitro clearance and computational data designed to aid medicinal chemists in achieving metabolically stable, permeable and potent drug candidates. Classifying compounds as permeable and stable and plotting molecular weight (MW) versus octanol: buffer (pH 7.4) distribution coefficients (log D) or estimated octanol: buffer (pH 7.4) distribution coefficients (elog D) reveals useful trends. Analysis of at least two orthogonal trends, such as permeability and clearance, can be extremely effective in balancing and optimizing multiple properties. In addition, molecular weight and log D impact potency-efficiency calculations, allowing potency, clearance and permeability to be optimized simultaneously. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5560 / 5564

页数：5

共 25 条

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