Design, synthesis and biological evaluation of 2,3-dihydroimidazo[2,1-b]thiazoles as dual EGFR and IGF1R inhibitors.
Bioorg Chem
; 115: 105151, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34333424
ABSTRACT
Herein we describe the design, synthesis and anticancer evaluation of a series of 2,3-dihydroimidazo[2,1-b]thiazoles as dual kinase inhibitors of IGF1R and EGFR. A series of saturated dihydroimidazo[2,1-b] thiazoles were synthesized to understand the structure-activity relationship. Further, the key modifications were performed to improve drug like properties of the series. A 2-oxa-6-azaspiro [3.3] heptane moiety was incorporated as a bioisosteric replacement of morpholine on dihydroimidazo[2,1-b] thiazole scaffold.Subsequent structure-activity relationship (SAR) studies identified several compounds with nM range of activity. The compound 18a shows promising activity, IC50 = 52 nM against IGF1R and IC50 = 35.5 nM against EGFR with descent PK profile. The identified leadshows promising activity against both wild type and the T790M mutant forms of enzymes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
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Desenho de Fármacos
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Receptor IGF Tipo 1
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Inibidores de Proteínas Quinases
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Imidazóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article