A multi-endpoint matched molecular pair (MMP) analysis of 6-membered heterocycles.
Bioorg Med Chem
; 25(1): 381-388, 2017 01 01.
Article
em En
| MEDLINE
| ID: mdl-27840138
ABSTRACT
Aromatic rings, ubiquitous in pharmaceutical compounds, are often exchanged with another ring during the optimization process of drug discovery. Inevitably, the preferred ring system for one endpoint may prove detrimental to another, thus necessitating a holistic, multiple endpoint optimization approach for finding the ideal replacement. Accordingly, we conducted an extensive matched molecular pair (MMP) analysis of common 6-membered aromatic rings across 4 endpoints critical for drug discovery (logD lipophilicity, microsomal metabolism, P-gp efflux and passive permeability). We also investigated the effect of context by considering the connecting atom. Heat maps were created as a simple yet comprehensive way to view and analyze the vast amount of interrelated data. Paired difference statistical tests were used to identify transforms with changes that were significantly different from zero. We conclude that the heat maps of transforms provide a unique and powerful approach for multiparameter optimization.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
/
Compostos Heterocíclicos com 1 Anel
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article