Optimization of the synthesis of BET BD2 selective inhibitor XY153.
Chem Biodivers
; 21(2): e202301584, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38163253
ABSTRACT
XY153 is a promising BET BD2 inhibitor with an IC50 value of 0.79â
nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains. However, the reported synthesis route of XY153 and its derivatives are extremely poor-yielding. After the synthesis of three key fragments, XY153 can only be obtained with a yield of 1.3 % in the original four-step reaction. In this study, we reported a three-step alternative route in the synthesis process of XY153. The reaction conditions for this route were thoroughly investigated and optimized, resulting in a significantly improved yield of 61.5 %. This efficient synthesis route establishes a robust chemical foundation for the rapid synthesis of XY153 derivatives as BET BD2 inhibitors in the near future.
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MEDLINE
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Fatores de Transcrição
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Antineoplásicos
Idioma:
En
Ano de publicação:
2024
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Article