Pyrazoles as non-classical bioisosteres in prolylcarboxypeptidase (PrCP) inhibitors.
Bioorg Med Chem Lett
; 24(7): 1657-60, 2014 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-24636945
ABSTRACT
Bioisosteres are integral components of modern pharmaceutical research that allow structural optimization to maximize in vivo efficacy and minimize adverse effects by selectively modifying pharmacodynamic, pharmacokinetic and physicochemical properties. A recent medicinal chemistry campaign focused on identifying small molecule inhibitors of prolylcarboxypeptidase (PrCP) initiated an investigation into the use of pyrazoles as bioisosteres for amides. The results indicate that pyrazoles are suitable bioisosteric replacements of amide functional groups. The study is an example of managing bioisosteric replacement by incorporating subsequent structural modifications to maintain potency against the selected target. A heuristic model for an embedded pharmacophore is also described.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Carboxipeptidases
/
Inibidores Enzimáticos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article