Discovery of pyridyl sulfonamide 11-beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors for the treatment of metabolic disorders.
Bioorg Med Chem Lett
; 24(21): 5045-9, 2014 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-25266782
ABSTRACT
A previous disclosure from this lab highlighted the discovery of pyridyl amides as potent 11ß-HSD1 inhibitors. In order to build additional novelty and polarity into this chemotype, replacement of the hydrogen-bonding carbonyl (CO) pharmacophore with the bioisosteric sulfonyl (SO2) group was examined. Despite initial comparisons suggesting the corresponding sulfonamides exhibited weaker activity versus their carbonyl counterparts, further optimization was performed in an effort to identify various potent and unique leads for the program. Judicious incorporation of polar moieties resulted in the identification of compounds with enhanced potency and lipophilicity profiles, resulting in leads with superior aqueous solubility and liver microsomal stability.
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01-internacional
Base de dados:
MEDLINE
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article