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BIBTEX RIS

Using the Golden Triangle to optimize clearance and oral absorption

2009; Elsevier BV; Volume: 19; Issue: 19 Linguagem: Inglês

10.1016/j.bmcl.2009.08.045

ISSN

1464-3405

Autores

Ted W. Johnson, Klaus Dress, Martin P. Edwards,

Tópico(s)

Analytical Chemistry and Chromatography

Resumo

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.

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