Synthesis and antiproliferative activity of a tetrahydrofuran analog of FR901464.
Bioorg Med Chem Lett
; 104: 129739, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38599298
ABSTRACT
FR901464 is a natural product that exhibits antiproliferative activity at single-digit nanomolar concentrations in cancer cells. Its tetrahydropyran-spiroepoxide covalently binds the spliceosome. Through our medicinal chemistry campaign, we serendipitously discovered that a bromoetherification formed a tetrahydrofuran. The tetrahydrofuran analog was three orders of magnitude less potent than the corresponding tetrahydropyran analogs. This study shows the significance of the tetrahydropyran ring that presents the epoxide toward the spliceosome.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piranos
/
Compostos de Espiro
/
Compostos de Epóxi
/
Furanos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article