Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives.
Bioorg Med Chem Lett
; 26(4): 1209-13, 2016 Feb 15.
Article
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| MEDLINE
| ID: mdl-26794040
ABSTRACT
The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure. Based on these changes, the pyrrolidine derivative 16 was identified as a suitable candidate compound and showed excellent pharmacokinetic profiles in rat and dog, while maintaining high levels of potency and selective antagonistic activity toward S1P2.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Derivados del Benceno
/
Receptores de Lisoesfingolípidos
Límite:
Animals
Idioma:
En
Año:
2016
Tipo del documento:
Article