Escape from adamantane: Scaffold optimization of novel P2X7 antagonists featuring complex polycycles.
Bioorg Med Chem Lett
; 27(4): 759-763, 2017 02 15.
Article
em En
| MEDLINE
| ID: mdl-28126517
ABSTRACT
The adamantane scaffold, despite being widely used in medicinal chemistry, is not devoid of problems. In recent years we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As an adamantane scaffold is a common structural feature in several P2X7 receptor antagonists, herein we report the synthesis and pharmacological evaluation of multiple replacement options of adamantane that maintain a good activity profile. Molecular modeling studies support the binding of the compounds to a site close to the central pore, rather than to the ATP-binding site and shed light on the structural requirements for novel P2X7 antagonists.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adamantano
/
Receptores Purinérgicos P2X7
/
Antagonistas do Receptor Purinérgico P2X
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2017
Tipo de documento:
Article