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Using the Golden Triangle to optimize clearance and oral absorption.

Abstract：

: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 (logD) or estimated octanol:buffer (pH 7.4) distribution coefficients (elogD) 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 logD impact potency-efficiency calculations, allowing potency, clearance and permeability to be optimized simultaneously.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Johnson TW,Dress KR,Edwards M

doi

10.1016/j.bmcl.2009.08.045

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

5560-4

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01185-8

journal_volume

19

pub_type

杂志文章

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