Scale-up and optimization of the synthesis of dual CBP/BRD4 inhibitor ISOX-DUAL.
Org Biomol Chem
; 20(19): 4021-4029, 2022 05 18.
Article
en En
| MEDLINE
| ID: mdl-35506991
ABSTRACT
ISOX-DUAL is a dual inhibitor of CBP/p300 (IC50 = 0.65 µM) and BRD4 (IC50 = 1.5 µM) bromodomains, and a useful chemical probe for epigenetic research. Aspects of the published synthetic route to this compound and its analogues are small-scale, poor-yielding or simply unamenable to scale-up without optimization. Herein we describe the development of a refined synthesis that circumvents the challenges of the original report, with notable improvements to several of the key synthetic transformations. Moreover, a general Suzuki Miyaura protocol for the late stage installation of alternative dimethyl-isoxazole acetyl-lysine (KAc) binding motifs is presented.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Nucleares
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido