Synthetic studies on mitotic kinesin Eg5 inhibitors: synthesis and structure-activity relationships of novel 2,4,5-substituted-1,3,4-thiadiazoline derivatives.
Bioorg Med Chem Lett
; 24(16): 3961-3, 2014 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-25001485
ABSTRACT
The 2,4,5-substituted-1,3,4-thiadiazoline derivative 1a has been identified as a new class of mitotic kinesin Eg5 inhibitor. With the aim of enhancement of the mitotic phase accumulation activity, structure optimization of side chains at the 2-, 4-, and 5-positions of the 1,3,4-thiadiazoline ring of 1a was performed. The introduction of sulfonylamino group at the side chain at the 5-position and bulky acyl group at the 2- and 4-position contributed to a significant increase in the mitotic phase accumulation activity and Eg5 inhibitory activity. As a result, a series of optically active compounds exhibited an increased antitumor activity in a human ovarian cancer xenograft mouse model that was induced by oral administration.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cinesinas
/
Inibidores Enzimáticos
/
Tiazolidinas
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article