High-throughput logPo/w determination from UHPLC measurements: Revisiting the chromatographic hydrophobicity index.
J Pharm Biomed Anal
; 127: 26-31, 2016 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-26732880
A fast and accurate lipophilicity determination is fundamental in the drug discovery process, as long as it is a relevant property in the absorption, distribution, metabolism, excretion and toxicity (ADMET) of a potential drug substance. In the present work, different models based on chromatographic retention values for a large set of compounds and some of their molecular descriptors (calculated by ACD/Labs or CODESSA programs) have been examined in order to establish reliable equations for logPo/w determination from fast chromatographic hydrophobicity index (CHI) measurements. This appears to be a very interesting high-throughput methodology for screening purposes, since CHI values can be measured by UHPLC in very short runs (<4min) and molecular descriptors can be easily computed from the structure of any compound. The selected final descriptors were Abraham's hydrogen-bond acidity (A) and excess molar refraction (E) from ACD/Labs, and hydrogen-bond acidity HDCA-1/TMSA and HOMO-LUMO polarizability descriptors from CODESSA software. The proposed equations allow an accurate determination of logPo/w with standard errors in the range of 0.4 units.
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01-internacional
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MEDLINE
Assunto principal:
Preparações Farmacêuticas
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Cromatografia Líquida
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Descoberta de Drogas
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Ensaios de Triagem em Larga Escala
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Modelos Químicos
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2016
Tipo de documento:
Article